Determination of the optimum definition of growth evaluation for indeterminate pulmonary nodules detected in lung cancer screening

OBJECTIVE: To determine the optimum definition of growth for indeterminate pulmonary nodules detected in lung cancer screening. MATERIALS AND METHODS: Individuals with indeterminate nodules as defined by volume of 50–500 mm(3) (solid nodules) and solid component volume of 50–500 mm(3) or average diameter of non-solid component ≥8 mm (part-solid nodules) on baseline lung cancer screening low-dose chest CT (LDCT) were included. The average diameters and volumes of the nodules were measured on baseline and follow-up LDCTs with semi-automated segmentation. Sensitivities and specificities for lung cancer diagnosis of nodule growth defined by a) percentage volume growth ≥25% (defined in the NELSON study); b) absolute diameter growth >1.5 mm (defined in the Lung-RADS version 1.1); and c) subjective decision by a radiologist were evaluated. Sensitivities and specificities of diagnostic referral based on various thresholds of volume doubling time (VDT) were also evaluated. RESULTS: Altogether, 115 nodules (one nodule per individual; 93 solid and 22 part-solid nodules; 105 men; median age, 68 years) were evaluated (median follow-up interval: 201 days; interquartile range: 127–371 days). Percentage volume growth ≥25% exhibited higher sensitivity but lower specificity than those of diametrical measurement compared to absolute diameter growth >1.5 mm (sensitivity, 69.2% vs. 42.3%, p = 0.023; specificity, 82.0% vs. 96.6%, p = 0.002). The radiologist had an equivalent sensitivity (53.9%; p = 0.289) but higher specificity (98.9%; p = 0.002) compared to those of volume growth, but did not differ from those of diameter growth (p>0.05 both in sensitivity and specificity). Compared to the VDT threshold of 600 days (sensitivity, 61.5%; specificity, 87.6%), VDT thresholds ≤200 and ≤300 days exhibited significantly lower sensitivity (30.8%, p = 0.013) and higher specificity (94.4%, p = 0.041), respectively. CONCLUSION: Growth evaluation of screening-detected indeterminate nodules with volumetric measurement exhibited higher sensitivity but lower specificity compared to diametric measurements.