Predictive Ability of CT Screen-Detected Nodule Volume, Diameter, and Volume-Doubling for Lung Cancer in NELSON Trial
The Dutch and Belgian NELSON trial is assessing the effect of increasing interval low-dose computed tomography (CT) screening for lung cancer on lung cancer mortality. In an analysis among screened Dutch participants reported in Lancet Oncology, Horeweg and colleagues identified screen-detected nodule volume, diameter, and volume doubling thresholds predictive of lung cancer.
Study Details
The NELSON trial is a randomized trial assessing the effect of low-dose CT screening with screening intervals of 1, 2, and 2.5 years vs no screening on lung cancer mortality. Of 15,822 participants enrolled in the trial, 7,915 are in the screening group and 7,907 in the no-screening group. The current analysis included 7,155 Dutch participants who underwent at least one round of screening.
Eligible participants were aged 50 to 75 years, had smoked ≥ 15 cigarettes per day for > 25 years or ≥ 10 cigarettes per day for > 30 years and were still smoking or had stopped smoking < 10 years previously. People with self-reported moderate or bad health, inability to climb two flights of stairs, body weight ≥ 140 kg, current or past renal cancer, melanoma, or breast cancer, lung cancer diagnosed < 5 years previously, or chest CT examination < 1 year previously were excluded.
Screening results were based on volumetry; initial results were classified as negative, indeterminate, or positive based on nodule presence and volume. Participants with an initial indeterminate result had follow-up screening to classify final results as negative or positive based on nodule volume-doubling time.
Data are from the first three rounds of screening and an additional 2 years of follow-up from the national cancer registry. Median follow-up was 8.16 years.
Lung Cancer Probabilities
A total of 9,681 noncalcified nodules were detected by CT screening in the 7,155 participants included in the analysis. Lung cancer probability was 0.4% (95% confidence interval [CI] = 0.3–0.6) in participants without nodules, which did not differ significantly from the probability of 0.6% (95% CI = 0·4–0·8, P = .17) in participants with nodule volume ≤ 100 mm³ or 0.4% (95% CI = 0.2–0.7, P = 1.00) in those with maximum transverse diameter < 5 mm.
Lung cancer probability was 2.4% (95% CI = 1.7–3.5) for nodules with volume of 100 to 300 mm³ and 1.3% (95% CI = 1.0–1.8) for those with diameter of 5 to 10 mm. For these nodules, probabilities were 0.8% (95% CI = 0.4–1.7) for volume-doubling times ≥ 600 days, 4.0% (95% CI = 1.8–8.3) for doubling times of 400 to 600 days, and 9.9% (95% CI = 6.9–14.1) for doubling times ≤ 400 days.
Cancer probability was 16.9% (95% CI = 14.1–20.0) for nodule volumes ≥ 300 mm³ and 15.2% (95% CI = 12.7–18.1) for those with diameter ≥ 10 mm.
Sensitivity and Specificity
Use of a simulated American College of Chest Physicians (ACCP) management protocol yielded a sensitivity of 90.9% and specificity of 87.2%. A diameter-based protocol with volumetry-based nodule diameter yielded sensitivity of 92.4% and specificity of 90.0%. A volume-based protocol yielded sensitivity of 90.9% and specificity of 94.9%.
The investigators concluded: “Small nodules (those with a volume < 100 mm³ or diameter < 5 mm) are not predictive for lung cancer. Immediate diagnostic evaluation is necessary for large nodules (≥300 mm³ or ≥ 10 mm). Volume doubling time assessment is advocated only for intermediate-sized nodules (with a volume ranging between 100-300 mm³ or diameter of 5-10 mm). Nodule management protocols based on these thresholds performed better than the simulated ACCP nodule protocol.”
The study was funded by Zorgonderzoek Nederland Medische Wetenschappen and Koningin Wilhelmina Fonds.
Nanda Horeweg, MD, of Erasmus University Medical Center, is the corresponding author for the Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
