Optimisation of volume-doubling time cutoff for fast-growing lung nodules in CT lung cancer screening reduces false-positive referrals

Objective: To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals. Methods: Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50-500 mm3), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference. Results: Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days. Conclusion: All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT ≤232 days. Lowering the VDT cutoff may reduce false-positive referrals. Key Points: • Lung nodules are common in CT lung cancer screening, most being benign • Short-term follow-up CT can identify fast-growing intermediate-size lung nodules • Most fast-growing nodules on short-term follow-up CT still prove to be benign • A new volume-doubling time (VDT) cut-off is proposed for lung screening • The optimised VDT cutoff may decrease false-positive case referrals for lung cancer

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