1. In a high-risk population, low-dose CT screening detected lung cancer with 84.6% sensitivity and 98.6% specificity.
2. Screen-detected cancers were found at earlier stages as compared to interval cancers not picked up on screening.
Evidence Rating: 1 (Excellent)
Study Rundown: The US Preventative Services Task Force has recommended annual low-dose CT screening for people at high risk for developing lung cancer. However, previous smaller studies have failed to show a survival benefit with this screening. In this study, over 7100 patients in the Netherlands were randomized to screening with increasing intervals or no screening. This pre-specified analysis did not include the non-screening arm, but examined solely the performance of low dose CT as a screening strategy. After a median follow-up time of 8.16 years, there were 196 screen-detected lung cancers and 35 interval lung cancers. This equated to a screening sensitivity of 84.6% and specificity of 98.6%; the positive and negative predictive values were 40.4% and 99.8%, respectively. Of the interval cancers, 35% were not visible on screening CT while the remainder was erroneously not diagnosed. Significantly, 83% of interval cancers were detected at stage III or IV while only 22% of screen-detected cancers were advanced at the time of diagnosis. Interval cancers were more likely to be small-cell carcinomas while screen-detected cancers were more likely to be adenocarcinomas. The results of this trial demonstrate that low does CT screening provides high sensitivity and specificity to detect early lung cancer in a high-risk population. However, the study is limited by a lack of survival data and comparison to the non-screening arm.
Relevant Reading: Lung cancer screening: achieving more by intervening less (The Lancet)
In-Depth [randomized controlled trial]: In this report, 7155 patients aged 50-75 years with a recent smoking history were included. All patients received low-dose CT screening at 1, 3, and 5.5 years and were followed up at a median duration of 8.16 years. Reflecting the high-risk population, 84% of participants were male and 55% were still currently smoking. A total of 187 (3%) participants were diagnosed with 196 screen-detected lung cancers during the follow-up period. Thirty-four (<1%) participants were diagnosed with 35 interval cancers. For all 3 screening events combined, sensitivity was 84.6% (95% CI: 79.6-89.2%) and specificity was 98.6% (95% CI: 98.5-98.8). The positive predictive value was 40.4% (95% CI: 35.9-44.7%) while the negative predictive value was 99.8% (95% CI: 99.8-99.9). Of the 35 interval cancers, 12 were determined retrospectively to not be visible on screening studies. Of the remaining undetected cases, diagnoses were missed primarily due to misinterpretation (50%), misclassification (6%), and participant non-compliance (6%). Eighty-three percent of interval cancers were Stage III or IV at diagnosis compared to 22% of screen-detected cancers (p < 0.0001).
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