Second Large Study Shows That Lung Cancer Screening Works

Pam Harrison

September 28, 2018

TORONTO — A second large trial has shown that a population-based lung cancer screening program significantly reduces mortality risk for high-risk former and current smokers.

New data from the NELSON study, conducted in the Netherlands and Belgium, show an even bigger reduction in deaths from lung cancer than was seen in the original landmark study, the National Lung Screening Trial (NLST), conducted in the United States.

The new data were presented here at the 19th World Conference on Lung Cancer (WCLC).

"Intensive screening is always a debatable issue, as people always have their opinions," NELSON investigator Harry de Konig, MD, PhD, professor of public health and screening evaluation, Erasmus Medical Center, Rotterdam, the Netherlands, told a press briefing here.

"But we showed that males at high risk for lung cancer have a reduced risk of dying from the disease," he said. The risk of dying from lung cancer among male participants was reduced by 26% in the screened arm in comparison with the control arm at 10 years' follow-up, he noted.

In the subset of women, which was smaller, the reduction was even greater, with the risk of dying from lung cancer reduced by 39% to 61% at various years of follow-up.

"So this type of screening results in a very substantial reduction in lung cancer deaths in both genders," he concluded.

Study Details

NELSON was a randomized, controlled, population-based screening trial for which individuals from population-based registries in the Netherlands and Belgium were recruited.

"To get to the final study population of about 16,000 people, we first had to send a general health questionnaire to 606,000 people," de Konig noted.

"And we selected those who met our eligibility criteria, namely, men and women aged 50 to 74 years and a smoking history of more than 10 cigarettes a day for more than 30 years or more than 15 cigarettes a day for more than 25 years," he added.

The average number of pack-years smoked in the overall cohort was approximately 40 years.

Slightly more than half of the participants were current smokers. Roughly 45% of participants had quit in the past 10 years, although they still met the requisite number of pack-years for study entry.

Some 7900 participants were randomly assigned to the screening arm, and another 7892 participants were assigned to the control arm.

Participants in the screening arm received a CT scan at baseline, 1 year later, 2 years later, and 2.5 years later, de Koning noted, for a total of four rounds of screening.

Uptake of screening was excellent for the first three rounds, though it dropped to about two thirds of the group assigned to the screening arm for the fourth round.

Investigators used volume and volume doubling time of nodules to determine test results.

At the end of the fourth round, a total of 27,053 screens had been performed.

Of these, test results were indeterminate for only 9.3% of the scans overall. Participants with indeterminate results were asked to come back and have the scan repeated.

However, de Koning emphasized that only 2.3% of participants in the screening arm required a referral for a repeat scan, suggesting that repeat scans did not create an undue burden on the healthcare system.

On the final analysis, 2.2% of the scan results were positive, yielding a 0.9% lung cancer detection rate overall.

"This means that if you had a positive test result and were referred [for another scan], your chances of having lung cancer was 41%," de Koning noted. "That was the positive predictive value on a positive result," he added.

Early-Stage Cancer

Most importantly, 50% of lung cancers detected during the screening program were very-early-stage IA cancers; 69% of screen-detected lung cancers were of stage IA or B.

Only 10% to 12% of those in the screening arm were diagnosed with stage IV disease.

This is in contrast to the usual diagnostic picture. According to the Dutch cancer registry, 50% of men are diagnosed with stage IV lung cancer, de Koning observed.

Among the male study participants, the numerical toll in lung cancer deaths at 10 years was 250, of which 157 occurred in the screening arm, giving a lung cancer mortality rate ratio of 0.74 at year 10 (P = .003), de Koning reported.

Even in the preceding 2 years, screening reduced the risk for death from lung cancer. The lung cancer mortality rate ratio was 0.75 in year 8 and 0.76 in year 9.

"In females, we saw an even more remarkable result," de Koning continued.

At year 10, screening reduced the risk for death from lung cancer by 39%. The lung cancer mortality rate was ratio 0.61 (P = .0543). In the 2 preceding years, screening reduced lung cancer mortality risk by 61% in year 8 and 53% in year 9. The lung cancer mortality rate ratio was 0.39 in year 8 and 0.47 in year 9.

"These findings show that CT screenings are an effective way to assess lung nodules in people at high risk for lung cancer," De Koning said in a press statement. It often leads to detection of suspicious nodules. With subsequent surgical intervention at relatively low rates and with few false positives, this screening "can positively increase the chances of cure in this devastating disease," he added.

NELSON is "the second largest trial in the world, with an even more favorable outcome than the first trial, the NLST, showed. These results should be used to inform and direct future CT screening in the world," he said.

Even Bigger Reduction Than Seen in NLST

The comparison with the NLST was highlighted by discussant John Field, MD, PhD, University of Liverpool, the United Kingdom.

He reminded the audience that the NLST demonstrated a 20% relative reduction in lung cancer mortality for annual screening over 3 years with low-dose CT compared to chest radiography.

At 10 years, Field calculated that CT screening in the NLST led to an 8% decrease in lung cancer mortality in men and a 27% decrease in women.

Given that mortality reductions at 10 years in the NELSON study were significantly greater than those seen in the NLST trial, "this demonstrates a major move forward in lung cancer screening," Field said.

This demonstrates a major move forward in lung cancer screening. Dr John Field

"There is now conclusive evidence for the implementation for lung cancer screening specifically for Europe based on two large randomized controlled trials," he concluded.

Annual Screening Recommended

Mainly on the basis of the results from the NLST, in 2013, the US Preventive Services Task Force recommended annual screening for lung cancer with low-dose CT for adults aged 55 to 80 years who have a 30 pack-year smoking history and who currently smoke or have quit within the past 15 years.

In addition, the task force noted that screening should be discontinued once a person has not smoked for 15 years or has developed a health condition that will substantially limit life expectancy or the ability or willingness to undergo curative lung surgery.

However, as previously reported, rates of lung cancer screening among current and former heavy smokers are very low in the United States and have remained unchanged despite recommendations for annual screenings in this high-risk group. In a study published in 2017 JAMA Oncology, the authors estimate that among 6.8 million smokers eligible for low-dose CT screening in 2015, only 262,700 (3.9%) received it.

De Konig has disclosed no relevant financial relationships. Dr Field has received speaker's bureau fees from Roche and speaker's fees from or has participated in advisory board consultations for Epigenomics and VIsionGate.

19th World Conference on Lung Cancer. Abstract PL02.05, presented September 25, 2018.

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