Lung cancer screening has been shown to significantly reduce lung cancer mortality, but some management protocols have more benefit than others, according to data presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC).¹

Although the Dutch-Belgian lung cancer screening trial Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) showed a reduction in lung cancer mortality of 24.0% for screening with low-dose computed tomography (CT), the National Lung Screening Trial (NLST) reduced lung cancer mortality by 20.0%. A model-based comparison of the two trials presented at the WCLC suggests that the nodule management protocol used in NELSON, which was based on volumetry as opposed to nodule diameter, has superior sensitivity and specificity.

Koen de Nijs

“Nodule management protocols based on volumetry are likely to increase the benefits of lung cancer screening, while reducing unnecessary follow-up procedures,” said Koen de Nijs, a PhD candidate at Erasmus University Medical Center in the Netherlands. “The higher CT sensitivity explains the favorable stage-shift and efficacy of the NELSON trial.”

Both NELSON and NLST were major CT screening trials powered to prove a mortality reduction from lung cancer, but there were several key differences between the studies. Although the NLST included three CT screens at 1-year intervals, NELSON had four screens at increasing intervals (from 1 year to 2.5 years apart). The trials also had different proportions of males and females and different smoking eligibility criteria. In addition, the two trials differed in the nodule management protocol. The NLST primarily used diameter to decide on follow-up procedures when a nodule was detected, whereas the NELSON trial used volume to determine the next step for patients.

As Mr. de Nijs explained, the distinction between nodule diameter and volume is still an active discussion among providers. The current Lung-RADS guidelines have adapted the diameter-based NLST protocol, whereas the British Thoracic Society guidelines recommend a volume-based NELSON protocol.

Study Methods

For this study, Mr. de Nijs and colleagues sought to determine the extent to which the more favorable stage-shift and larger efficacy of the NELSON trial was attributable to differences in CT sensitivity. In addition to the increased mortality reduction from lung cancer, the NELSON trial improved the percentage of stage IA and IB cancers detected compared to the NLST (71% vs 62%).

The researchers used the MISCAN-Lung model, which had previously informed 2013 and 2021 U.S. Preventive Services Taskforce guidelines, to replicate the Dutch part of the NELSON trial, as previously done for the NLST. MISCAN estimates the total number of detectable cancers at each screening round, by stage and histology. Mr. de Nijs and colleagues also controlled for the characteristics of the study population, trial design, and lung cancer epidemiology in each trial.

NELSON Protocol More Sensitive

The researchers found that the sensitivity in NELSON was estimated to be higher across all stages compared with the NLST. Importantly, said Mr. de Nijs, CT sensitivity was considerably higher for early-stage disease, “which are the cancers we want to detect.”

For stage IA lung adenocarcinoma, for example, the estimated CT sensitivity was 73% in NELSON vs 57% in the NLST, and for stage IB adenocarcinoma, the sensitivity was 90% vs 64%, respectively. For stage IA and IB squamous cell carcinoma, the benefit was less pronounced (approximately 5%), but for stage II squamous cell carcinoma, the sensitivity was 75% in NELSON compared to 39% in the NLST.

“This model-based comparison of the NELSON and NLST suggests that the differences in screening effectiveness may be explained by differences in the nodule management protocols,” said Mr. de Nijs. “The protocol used in NELSON was more sensitive than the protocol used in the NLST, particularly for early-stage cancers. Furthermore, the protocol used in NELSON also had improved specificity.”

He concluded: “Volume-based nodule management may improve the potential for lung cancer mortality reduction in population-based screening programs.” 

DISCLOSURE: Dr. de Nijs reported no conflicts of interest.

REFERENCE

1. de Nijs K, ten Haaf K, van der Aalst CM, et al: 2022 World Conference on Lung Cancer. Abstract OA05.04. Presented August 7, 2022.