Relationship between the number of new nodules and lung cancer probability in incidence screening rounds of CT lung cancer screening: The NELSON study

Background: New nodules are regularly found after the baseline round of low-dose computed tomography (LDCT) lung cancer screening. The relationship between a participant's number of new nodules and lung cancer probability is unknown. Methods: Participants of the ongoing Dutch-Belgian Randomized Lung Cancer Screening (NELSON) Trial with (sub)solid nodules detected after baseline and registered as new by the NELSON radiologists were included. The correlation between a participant's new nodule count and the largest new nodule size was assessed using Spearman's rank correlation. To evaluate the new nodule count as predictor for new nodule lung cancer together with largest new nodule size, a multivariable logistic regression analysis was performed. Results: In total, 705 participants with 964 new nodules were included. In 48% (336/705) of participants no nodule had been found previously during baseline screening and in 22% (154/705) of participants > 1 new nodule was detected (range 1-12 new nodules). Eventually, 9% (65/705) of the participants had lung cancer in a new nodule. In 100% (65/65) of participants with new nodule lung cancer, the lung cancer was the largest or only new nodule at initial detection. The new nodule lung cancer probability did not differ significantly between participants with 1 (10% [56/551], 95%CI 8-13%) or > 1 new nodule (6% [9/154], 95%CI 3-11%, P=.116). An increased number of new nodules positively correlated with a participant's largest nodule size (P<0.001, Spearman's rho 0.177). When adjusted for largest new nodule size, the new nodule count had a significant negative association with lung cancer (odds ratio 0.59, 0.37-0.95, P=.03). Conclusion: A participant's new nodule count alone only has limited association with lung cancer. However, a higher new nodule count correlates with an increased largest new nodule size, while the lung cancer probability remains equivalent, and may improve lung cancer risk prediction by size only.