Results of the two rounds of annual incidence screening with low-dose computed tomography (CT) vs radiography in the National Lung Screening Trial (NLST) were recently reported by Denise R.
Aberle, MD, Professor of Radiology and Bioengineering at the University of California at Los Angeles and national principal investigator for the NLST, and colleagues in The New England Journal of Medicine. Among the findings of the trial is that three annual low-dose CT screens detected more lung cancers, more early-stage lung cancers, and fewer late-stage lung cancers relative to radiography screening, albeit with a slightly lower positive predictive value.

The NLST was conducted to determine whether three annual screenings (prevalence round T0 and incidence rounds T1 and T2) with low-dose helical CT can reduce mortality from lung cancer compared with chest radiography in an asymptomatic high-risk population of individuals 55 to 74 years old with a history of at least 30 pack-years of smoking. The current analysis involved findings from the first two incidence screenings (rounds T1 and T2).

T1 Screening Round Results

At the T1 round, 24,715 (94%) of 26,285 eligible participants underwent CT screening, with positive results found in 27.9%. Of 26,410 eligible for radiography screening, 24,089 (91%) were screened, with positive results in 6.2%.

In the CT group, 186 participants were diagnosed with lung cancer, including 168 of 6,901 participants with positive screening results, 10 of 17,814 with negative screening results, 6 of 1,570 who were not screened at T1, and 2 of 437 ineligible participants with lung cancers that were first diagnosed during the T1 screening year.

In the radiography group, 133 participants were diagnosed with lung cancer, including 65 of 1,482 with positive screening results, 44 of 22,607 with negative screening results, 21 of 2,321 who were not screened, and 3 of 322 ineligible participants with lung cancers diagnosed during the T1 screening year.

For the CT vs radiography groups, sensitivity was 94.4% vs 59.6%, specificity was 72.6% vs 94.1%, positive predictive value was 2.4% vs 4.4%, and negative predictive value was 99.9% vs 99.8%.

T2 Screening Round Results

At the T2 round, 24,102 (93%) of 25,942 eligible participants underwent CT screening, with positive results found in 16.8%. Of 26,110 eligible for radiography screening, 23,346 (89%) underwent screening, and positive results were found in 5.0%.

In the CT group, 237 participants were diagnosed with cancer, including 211 of 4,054 with positive screening results, 16 of 20,048 with negative screening results, 7 of 1,840 who were not screened at T2, and 3 of 780 ineligible participants with lung cancers diagnosed during the T2 screening year.

In the radiography group, 144 participants received a diagnosis of lung cancer, including 78 of 1,174 with positive screening results, 44 of 22,172 with negative screening results, 18 of 2,764 who were not screened, and 4 of 622 participants who were ineligible for the T2 screening but received a diagnosis of lung cancer during the T2 screening year.

For the CT vs radiography groups, sensitivity was 93.0% vs 63.9%, specificity was 83.9% vs 95.3%, positive predictive value was 5.2% vs 6.7%, and negative predictive value was 99.9% vs 99.8%.

Stages of Identified Cancers

Among lung cancers of known stage at T1, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group, and 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV in the radiography group. The differences in stage distribution between groups persisted at T2.

The increase in early-stage lung cancers in the CT group was associated with a decrease in late-stage lung cancers. Over the course of the trial, the incidence of stage IV lung cancer was 138 cases per 100,000 person-years in the CT group vs 204/100,000 person-years in the radiography group (rate ratio = 0.68, 95% confidence interval = 0.57– 0.80).

Relationship of Nodule Size to Cancer

Nodule size among patients with lung cancers diagnosed with CT screening at T1 was 4 to 10 mm in diameter in 34.5%, 11 to 20 mm in 44.0%, 21 to 30 mm in 11.9%, and > 30 mm in 4.8%. The positive predictive value for detection of a nodule of any size with CT at T1 was 2.4%, increasing to 58.2% for positive screening results with subsequent biopsy. For nodules 4 to 6 mm in diameter, the positive predictive value at T1 was 0.3%.

In the radiography group, the largest nodule or mass observed among 65 lung cancers detected at T1 was 4 to 10 mm in diameter in 13.8%, 11 to 20 mm in 33.8%, 21 to 30 mm in 24.6%, and > 30 mm in 15.4%. The positive predictive value for detection of a nodule of any size at T1 in the radiography group was 4.4%, increasing to 67.4% for positive screening results with subsequent biopsy.

In both groups, the positive predictive value for detection of a nodule increased as nodule size increased from 4 to 30 mm. In the radiography group, the positive predictive value for nodules smaller than 4 mm was relatively high; it is unclear whether these nodules corresponded to a lung cancer or prompted follow-up assessments that led to a diagnosis of lung cancer.

In both groups, detection of masses larger than 30 mm had a slightly decreased positive predictive value relative to the detection of nodules that were 21 to 30 mm, likely representing interpretation of pneumonia as a positive screening result.

Histology

The most common histologic types of lung cancer in both screening groups at both screenings were adenocarcinoma, accounting for 36.6% of cancers in the CT group and 32.8% in the radiography group at T1 and 34.9% and 33.1%, respectively, at T2. Squamous cell carcinoma accounted for 21.0% of cancers in the CT group and 22.9% in the radiography group at T1 and 26.0% and 23.9%, respectively, at T2.

In the CT group, lung cancers characterized as bronchioloalveolar cell carcinoma were predominantly diagnosed after a positive screening and accounted for 17.3% and 13.3% of lung cancers detected on positive screening at T1 and T2, respectively. Few bronchioloalveolar cell carcinomas were diagnosed in the radiography group, likely reflecting difficulty in discerning these lesions on planar imaging.

Small cell carcinoma was detected with similar frequency in both groups at both screenings, but was more commonly detected in CT participants with positive results vs those with negative results. The converse was true in the radiography group.

The investigators concluded, “Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed.” ■

Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit www.nejm.org.

Reference

1. Aberle DR, DeMello S, Berg CD, et al: Results of the two incidence screenings in the National Lung Screening Trial. N Engl J Med 369:920-931, 2013.