Persisting new nodules in incidence rounds of the NELSON CT lung cancer screening study

Background The US guidelines recommend low-dose CT (LDCT) lung cancer screening for high-risk individuals. New solid nodules after baseline screening are common and have a high lung cancer probability. Currently, no evidence exists concerning the risk stratification of non-resolving new solid nodules at first LDCT screening after initial detection. Methods In the Dutch-Belgian Randomized Lung Cancer Screening (NELSON) trial, 7295 participants underwent the second and 6922 participants the third screening round. We included participants with solid nodules that were registered as new or <15 mm³ (study detection limit) at previous screens and received additional screening after initial detection, thereby excluding high-risk nodules according to the NELSON management protocol (nodules ≥500 mm 3 ). Results Overall, 680 participants with 1020 low-risk and intermediate-risk new solid nodules were included. A total of 562 (55%) new solid nodules were resolving, leaving 356 (52%) participants with a non-resolving new solid nodule, of whom 25 (7%) were diagnosed with lung cancer. At first screening after initial detection, volume doubling time (VDT), volume, and VDT combined with a predefined ≥200 mm 3 volume cut-off had high discrimination for lung cancer (VDT, area under the curve (AUC): 0.913; volume, AUC: 0.875; VDT and ≥200 mm 3 combination, AUC: 0.939). Classifying a new solid nodule with either ≤590 days VDT or ≥200 mm 3 volume positive provided 100% sensitivity, 84% specificity and 27% positive predictive value for lung cancer. Conclusions More than half of new low-risk and intermediate-risk solid nodules in LDCT lung cancer screening resolve. At follow-up, growth assessment potentially combined with a volume limit can be used for risk stratification. Trial registration number ISRCTN63545820 ; pre-results.