We report the prevalence of abnormalities in the NLST population at the onset of screening.8
As expected, more positive screening results, more diagnostic procedures, more biopsies and other invasive procedures, and more lung cancers were seen in the low-dose CT group than in the radiography group during the first screening round. In addition, more early-stage lung cancers, but similar numbers of late-stage cancers, were diagnosed in the low-dose CT group.
Our findings for screening with the use of low-dose CT are similar to those in previous large studies of low-dose CT screening (Early Lung Cancer Action Project [ELCAP],22
International Early Lung Cancer Action Program [I-ELCAP],23
Lung Screening Study Feasibility Phase,26
and NELSON [Current Controlled Trials number, ISRCTN63545820]28
). The ages and smoking histories of our participants were similar to those of participants in most of these studies. In addition, the sensitivity (93.8%), specificity (73.4%), rate of positive screening results (27.3%), and positive predictive value (3.8%) of low-dose CT were in the midrange of the corresponding values in the previous studies, as was the proportion of participants who underwent biopsy (1.9%).
Two additional findings suggest that screening by means of low-dose CT was well implemented in our study. The compliance rate of 98.5% was much higher than the 85% rate that was assumed for each screening round in our sample-size calculation, and only four of the low-dose CT scans were judged to be nondiagnostic.
The high rate of positive screening results (and the low positive predictive value) with low-dose CT resulted in the performance of many diagnostic procedures. Nonetheless, the number of follow-up chest CT scans per positive screening result in the low-dose CT group was modest — approximately 1 scan per positive screening result (i.e., 7288 CT scans performed per 7049 participants with a positive result of low-dose CT scanning). A recent cost-effectiveness analysis of lung-cancer screening29
assumed, for the baseline case, that nodules 4 to 8 mm (presumably in the longest diameter) would be evaluated by means of serial CT at 3, 6, and 9 months, on the basis of the protocol for the Mayo study,30
which started in 1999. Subsequent reports have recommended less frequent follow-up CT, as reflected in our trial, which should improve the cost-effectiveness of the procedure in the face of its high rate of positive results.
Some of our findings with respect to the initial low-dose CT screening are not fully consistent with those reported previously. The prevalence of lung cancer (1.1%) is at the low end of the reported range in prior large studies of participants with similar smoking histories (1.0 to 2.8%) but is close to the rate of 1.0% in the NELSON trial, the most recent study that is comparable to ours. This low rate may be due to some combination of the following factors: the healthy-volunteer effect (volunteers in trials are healthier than the general population), a younger population in our study than in the most recent studies, the high proportion of former smokers in our study, and the limitations of lung-cancer prediction estimates that are based on pack-years.31
The proportion of all lung cancers classified as stage I (55%) was also low relative to the range reported in other studies (54 to 85%), but this may be partly due to exclusion of small-cell cancer in the other studies and the more frequent use of PET-CT to ascertain the cancer stage in our study. Adenocarcinoma was the most common histologic finding in both our study and previous studies. Bronchioloalveolar carcinoma occurred about twice as frequently in our study (with a rate of 13%) than in others, possibly because of higher spatial resolution of the screening procedure and more frequent reporting of this type of carcinoma. Bronchioloalveolar carcinoma is no longer reported in many centers, on the basis of recent recommendations,32
and may soon be only of historical interest.
The results of chest radiography in our study were also similar to those in the comparable subgroup of participants in the PLCO radiography group.10
In our radiography group and the PLCO radiography subgroup, 9.2% and 11.0% of participants, respectively, had positive screening results; 0.7% and 0.8% underwent biopsy; and 0.5% and 0.6% had lung cancer detected on screening; the sensitivity in the respective groups was 74% and 77%, the specificity was 91% and 90%, and the positive predictive value was 5.7% and 5.5%. These similarities suggest that more important outcomes, including mortality from lung cancer, should also be similar.
Several limitations of our study deserve discussion. Our participants were similar to the general population of smokers in the United States except for a higher proportion of former smokers and a higher educational level, which may partly explain the lower prevalence of lung cancer in our study than in other studies. This suggests that caution should be used in generalizing other results of the initial round of screening in our study to the U.S. population of smokers. In addition, because the numbers of follow-up procedures were counted only in participants with positive screening results, they undoubtedly underestimate the frequency of diagnostic procedures performed because of a screening result (e.g., procedures performed to investigate potentially clinically significant abnormalities). Finally, because mortality was not reduced by screening with chest radiography among the PLCO participants who were comparable to our participants,10
the anticipated comparison of the results of our first round of low-dose CT screening with no screening in the ongoing NELSON trial should be of great interest.