Imaging Features Suggestive of Multiple Primary Lung Adenocarcinomas

The tumor-node-metastasis classification system has proposed that lung cancers presenting as multifocal ground-glass nodules (multi-GGN) on computed tomography scan should be staged as multiple primaries instead of intrapulmonary metastases. However, the problem still exists for those synchronous multiple lung adenocarcinomas (SMLA) involving solid lesions. This study aimed to explore the distinct features of SMLA to better define the diagnosis and staging of this disease.

Between 2008 and 2016, consecutive patients with complete resection of SMLA were prospectively enrolled in the study. The patients were divided into three groups based on CT images as follows: multi-GGN, one solid nodule plus one or more GGNs (solid-GGN), and multiple solid lesions with or without GGN (multi-solid). Clinicopathologic features and survival outcomes were compared between these groups. Multivariate Cox proportional hazards analyses using bootstrap internal validation were performed to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS).

Of the 695 patients who met the inclusion criteria, 486 (69.9%) presented with multi-GGN tumor, 124 (17.9%) with solid-GGN tumor, and 85 (12.2%) with multi-solid tumor. The three groups had distinguished clinicopathologic features of gender, smoking history, nodal metastases, tumor size, subtype, and location (all P < 0.001). Multivariate analyses demonstrated that multi-solid tumor was an independent predictor for both decreased RFS [hazard ratio (HR) 2.941; 95% confidence interval (CI) 1.07-8.08; P = 0.036] and poor OS (HR 6.13; 95% CI 1.15-32.63; P = 0.034), but neither RFS (P = 0.384) nor OS (P = 0.811) differed between solid-GGN and multi-GGN tumors.

Both multi-GGN and solid-GGN tumors should be staged as multiple primaries, whereas multi-solid tumor was indicated to be advanced disease.