Low-dose lung cancer screening by computed tomography (CT) is associated with a 16% relative reduction in lung cancer mortality over no lung cancer screening of high-risk individuals, based on a meta-analysis conducted by investigators with the United Kingdom Lung Cancer Screening (UKLS) trial.1
During the International Association for the Study of Lung Cancer (IASLC) 2021 World Conference on Lung Cancer, UKLS lead investigator John Field, PhD, FRCPath, of the Department of Molecular and Clinical Cancer Medicine at the University of Liverpool in the United Kingdom, presented the latest results of the
John Field, PhD, FRCPath
UKLS study along with a meta-analysis that incorporated data from similar trials, such as the two largest—the National Lung Screening Trial (NLST)2 and the Dutch-Belgian Lung Cancer Screening trial, NELSON.3 The findings were simultaneously published in The Lancet Regional Health—Europe.4
In the UKLS trial, which used Wald single-screen design with low-dose CT, the investigators reported a mortality reduction of 35% (relative risk [RR] = 0.65; 95% confidence interval [CI] = 0.41–1.02; P = .062). This finding did not meet statistical significance but is “consistent with the findings from other trials, of a substantial reduction in lung cancer mortality,” Dr. Field commented.
Findings from the meta-analysis, however, were statistically significant, showing a 16% reduction in lung cancer mortality. The NLST and NELSON trials had also shown significant risk reductions—20% in the NLST; 24% in males in the NELSON trial (and 33% in women, which was not significant).
The most recent UKLS and meta-analysis data provide the impetus to put in place lung cancer screening programs internationally, he said, and especially to encourage nations in Europe to start their own implementation programs. “We have reached the point where we have sufficient data, in my mind, to move forward with the internationalimplementation of lung cancer CT screening,” Dr. Field commented.
Results at 7 Years
Researchers analyzed a total of 1,987 UKLS participants in the intervention arm and 1,981 in the usual-care arm and followed them for a median of 7.3 years. The results showed a nonsignificant reduction in lung cancer mortality (RR = 0.65; 95% CI = 0.41–1.02; P = .062) based on 30 lung cancer deaths in the screening arm and 46 in the control arm. These results were similar for males (RR = 0.63) and females (RR = 0.63). The (nonsignificant) difference emerged most strongly 3 to 6 years after randomization and continued for the 7-year follow-up period, he added.
There were 512 deaths from any cause: 246 in the screening arm and 266 in the control arm. This difference also was not significant (RR = 0.91; 95% CI = 0.77–1.09).
Of note, screened patients had more tumors diagnosed at an early stage. As the authors wrote in The Lancet Regional Health—Europe: “The fundamental basis on which one undertakes lung cancer screening is to identify early lung cancer when it is still readily curable.” To this end, the UKLS Wald single-screen design resulted in a diagnosis of lung cancer at stage I for 67% of participants, with 83% suitable for surgical intervention (P < .001), Dr. Field reported.
Meta-analysis Performed
“The UKLS pilot study was not powered to provide mortality data. The relative risk value of 0.65 is very encouraging, but it is not statistically significant (95% CI = 0.41–1.02). For that very reason, we undertook a -meta-analysis,” Dr. Field explained.
The meta-analysis indicated a significant reduction in lung cancer mortality, with a pooled overall relative rate of 0.84 (95% CI = 0.76–0.92) from the nine eligible trials included in the analysis. The study found no significant heterogeneity (P = .31; I2 = 14.2%) and a small relative reduction in all-cause mortality (RR = 0.97; 95% CI = 0.94–1.00).
“The lung cancer mortality lung figure of 16% is very conservative, as discussed in our study publication, for a range of reasons,” he commented.
“The Wald single-screen design allows us to demonstrate the continued benefits of lung cancer [low-dose] CT screening beyond the initial screen,” Dr. Field said, elaborating in the press briefing that the single-screen design “was excellent” for this clinical trial. However, in real-world screening, it would more likely be performed on a yearly basis or possibly biennially, dependingon the patient’s CT report(s) and their known risk factors.
About the UKLS
The UKLS is a randomized controlled trial, comparing low-dose CT screening with usual care in a high-risk population selected using the Liverpool Lung Project (LLPv2) risk model. It also had a unique Wald single low-dose CT screening design, in a high-risk population.
The LLPv2 risk model is a modified version of the published LLP model, which incorporates age, smoking duration, family history of lung cancer, history of malignancies and respiratory diseases (pneumonia, bronchitis, emphysema, tuberculosis, chronic obstructive pulmonary disease) and exposure to asbestosis. The LLPv2 risk model treats cigar and pipe smoking as conferring an identical risk to cigarette smoking.
KEY POINTS
- An update of the United Kingdom Lung Cancer Screening trial (UKLS) found a 35% nonsignificant reduction in lung cancer mortality with low-dose CT; the study was not powered for this endpoint.
- Investigators performed a meta-analysis of nine screening trials and showed a 16% statistically significant reduction in lung cancer mortality with low-dose CT.
- The findings from many screening trials are consistent on the finding that screening reduces lung cancer deaths.
- Efforts should now be directed toward international implementation.
The study randomly allocated 4,055 participants between 2011 and 2013 to undergo a single low-dose CT screening or no screening (usual care). Data were collected on lung cancer cases and deaths to February 29, 2020, through linkage to UK national registries.
The uniqueness of the UKLS lies in the fact that it was the only randomized screening trial to use a formal, multivariate lung cancer risk-prediction model to select high-risk participants (high risk = 4.5% risk over 5 years).
DISCLOSURE: Dr. Field has served on the speakers bureau of AstraZeneca and the advisory boards of Epigenomics, Nucleix Ltd, AstraZeneca, iDNA; and has received grant support from Janssen Research & Development, LLC.
REFERENCES
1. Field JK, Vulkan D, Davies MPA, et al: UKLS trial outcome results: Lung cancer mortality reduction by LDCT screening confirmed in an international meta-analysis. 2021 World Conference on Lung Cancer. Abstract OA19.02. Presented September 12, 2021.
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 365:395-409, 2011.
3. De Koning HJ, van der Aalst CM, de Jong PA, et al: Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med 382:503-513, 2020.
4. Field JK, Vulkan D, Davies MPA, et al: Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Regional Health—Europe. September 11, 2021 (early release online).
