Lung Cancer Risk Associated With New Solid Nodules in the National Lung Screening Trial

OBJECTIVE. As low-dose CT (LDCT) lung cancer screening moves into routine clinical practice, evaluation of nodules identified as new becomes critical. We examine the frequency and clinical outcomes of new lung nodules reported at the two postbaseline annual screening examinations (hereafter referred to as postbaseline time 1 [T1] and time 2 [T2]), compared with those detected at baseline in the National Lung Screening Trial. MATERIALS AND METHODS. Radiologists classified nodules detected at T1 and T2 as new or preexisting on the basis of comparison with findings from prior LDCT screening examinations. Subjects were tracked for lung cancer incidence and mortality. We examined the incidence of new nodules and their associated lung cancer risk by nodule size (i.e., mean diameter). RESULTS. A total of 25,002 subjects underwent the baseline LDCT screening examination and either a T1 or T2 LDCT screen. At both T1 and T2, 2.6% of subjects had new solid nodules. Of the new solid nodules, 53.0% were < 6 mm, 29.5% were 6 to < 10 mm, and 17.1% were >= 10 mm. Lung cancer risk (defined as diagnosis within 2 years of baseline) increased from 1.1% for nodules < 4 mm to 24.0% for those >= 20 mm. Compared with solid nodules detected at baseline, the cancer risk was higher for new solid nodules that were 4 to < 6 mm (p < 0.001) and 6 to < 8 mm (p < 0.001) but lower for new nodules >= 20 mm (p = 0.03). Cancers associated with new nodules had significantly poorer survival than did those associated with baseline nodules and were significantly less likely to be adenocarcinoma. CONCLUSION. The incidence of new nodules was 2-3% annually, with the cancer risk increasing by nodule size. New nodules may convey differential lung cancer risks by size, compared with baseline nodules.