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Lung cancer is associated with high morbidity and mortality. In 2018, the estimated number of new cases of lung cancer in the United States alone was 234,030 (121,680 in men and 112,350 in women), and the number of deaths was 154,050 (83,550 in men and 70,500 in women).1 The National Lung Screening Trial (NLST), launched in 2002, reported reduced lung-cancer mortality in patients undergoing low-dose computed tomographic (CT) screening.2 The trial enrolled more than 53,000 heavy smokers and reported 20% fewer lung cancer deaths among trial participants in the intervention group.2 However, the majority of nodules detected by CT were benign, requiring interval follow-up or biopsies for definitive diagnosis. As the NELSON trial recently reported, fewer than 1% of newly diagnosed subsolid nodules are malignant, and only 6% of participants with a new subsolid nodule have early lung cancer (adenocarcinoma in situ).3

The implementation of lung cancer screening heralded a new era for the treatment of early lung cancer. However, many of the newly identified lung nodules were benign or too small to warrant definitive diagnosis based on imaging acquired at a single point in time. Hence, a large number of these nodules had to be followed until they demonstrated growth or were amenable to successful biopsy, and there was widespread concern that this would pose a potentially large and technically challenging diagnostic burden on the healthcare system.4

The management of pulmonary nodules is driven by size, radiographic appearance, and growth rate. The criteria proposed by the Early Lung Cancer Project study group5 recommend biopsy and/or surgical resection for nodules greater than 1 cm and follow-up CT scans for smaller lesions to demonstrate stability. Both the Fleischner Society6,7 and the American College of Radiology (Lung-RADS)8 (see Chapter 3) recommend serial CT follow-up of subcentimeter pulmonary nodules, with intervention reserved for nodules suspicious for lung cancer. Similar criteria apply to ground glass opacities (GGO). These nodules are less distinct, may represent carcinoma in situ or early adenocarcinoma, and are usually followed longitudinally by CT until they grow sufficiently dense and/or large to be considered suspicious for invasive malignancy.6 Even nodules that appear suspicious on imaging are challenging from a management perspective, as they are difficult to biopsy and palpate using traditional surgical techniques. These nodules must be followed via serial imaging until they are large enough to be deemed resectable, in some cases requiring a lobectomy. Since some of these nodules may represent early lung cancer, a resection could be curative. Therefore, newer techniques that can effect a surgical resection with optimal margins, lessoning the burden of continued surveillance, are needed.

Under the current standard of care, the pathologic diagnosis of lung nodules is accomplished either with image-guided biopsy or using navigational bronchoscopic techniques, where the diagnostic yield is proportional to the size of the nodule (e.g., 90% for 3-cm diameter vs. ...

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