Lynn T. Tanoue


Curr Opin Pulm Med. 2016;22(4):327-335. 

In This Article

Benefit of Screening

The landmark National Lung Screening Trial (NLST) was the first published randomized controlled trial (RCT) to demonstrate a mortality benefit with LDCT screening.[16] The NLST and two other RCTs, the Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays (DANTE) trial[17,18] and the Danish Lung Cancer Screening Trial (DLCST)[19] informed the USPSTF recommendation supporting.screening[20,21] This evidence base is dominated by the NLST, which is by far the largest RCT, a distinction it will likely retain. The NLST enrolled 53 454 individuals who were ages 55–74 years, had at least a 30 pack-year smoking history, and were either currently smoking or had quit within the prior 15 years. Study participants were randomized to either LDCT or CXR annually for 3 years; median follow-up duration was 6.5 years. The primary end point was a 20% decrease in lung cancer mortality in the LDCT arm compared with the CXR arm. The NLST was terminated early when it was determined that this end point would be met. Figure 1, from the NLST, demonstrates that more lung cancers were diagnosed in the group randomized to LDCT screening, but resulted in fewer cancer deaths. In practical terms, the 20% relative reduction in mortality from lung cancer related to screening with LDCT translates into an absolute risk reduction of lung cancer death from 1.66 to 1.33%, or three fewer deaths per 1000 persons screened.

Figure 1.

Cumulative numbers of lung cancers and of deaths from lung cancer. The number of lung cancers (panel A) includes lung cancers that were diagnosed from the date of randomization through 31 December 2009. The number of deaths from lung cancer (panel B) includes deaths that occurred from the date of randomization through 15 January 2009. Reproduced with permission from [16].

Other RCTs performed around the world have also focused on middle-aged and older persons with heavy and proximate cigarette exposure. These studies consistently demonstrate that the majority of LDCT screening-identified lung cancers are early stage, in contrast to usual care where approximately two-thirds of cancers are advanced stage at diagnosis[16–19,22–25] as demonstrated in Table 1. One of the basic tenets of screening, detection of disease at early stage when treatment is more beneficial, is thus satisfied. However, the gold standard of effective screening is a decrease in disease-related mortality in the population being screened. The major limitation of most lung cancer screening trials has been power sufficient to detect a reasonable reduction in mortality. For example, the DANTE trial, with 2472 study participants, would have achieved significance only if a 50% relative mortality difference between its two arms had been observed.[17,18] Of the completed trials in Table 1, only NLST, with study participant enrollment of more than 50 000 persons, demonstrated a mortality benefit. This points out the difficulty of establishing with reasonable certainty any mortality benefit of lung cancer screening, as the sheer scale of trials capable of measuring an effect is daunting. With this issue in mind, there is great interest in the ongoing Nederlands-Leuvens Longkanker Screenings Onderzoek (Dutch-Belgian Randomized Lung Cancer Screening Trial, NELSON).[24,25] NELSON, with an enrollment of 15 822 persons, has sufficient power to detect a 25% reduction in lung cancer mortality over 10 years of follow-up, with results expected shortly.

One other important potential benefit from lung cancer screening relates to tobacco treatment. Smoking cessation is a more powerful intervention in preventing lung cancer than screening.[26] All RCTs in Table 1 included tobacco treatment in both arms, but many participants in these trials continued to smoke. Younger age, lower socioeconomic status, spouseless status, lower BMI, higher smoking intensity and duration, and ongoing secondhand smoke exposure are known to be associated with continued smoking.[27] There has been debate about the impact of screening on smoking cessation. One concept is that screening creates a 'teachable moment' in a motivated individual; conversely, concern has been raised that active smokers who have a normal screen may feel validated to continue smoking (the 'health certificate' effect). A recent subanalysis of the NLST demonstrated that smoking cessation was strongly associated with the degree of abnormality on the screening study; the higher the concern for lung cancer, the more likely smoking cessation would occur.[28] Overall, a 6% lower rate of smoking was observed in groups with abnormal screens compared with those with normal results. However, over 7 years of follow-up, there was a substantial decline in smoking prevalence across all groups, including those with normal screens. This supports the concept of the 'teachable moment', and emphasizes the importance of tobacco treatment in lung cancer screening programs.