Abstract

Objectives: Identification of synchronous non-small-cell lung cancers (NSCLC) is important for both therapeutic and prognostic purposes. The aim of this study was to investigate the strategy using the new histologic classification and driver-mutational testing to define multi-primary lung cancers. Methods: A prospectively-collected data of patients treated for synchronous NSCLC was retrospectively analyzed. Cases were defined using Martini-Melamed criteria, and validated by histologic subtyping and driver mutation of selected genes. Kappa coefficient was calculated to evaluate the consistency between the diagnostic methods. Survival was estimated between patients with primary and metastatic tumours controlling by nodal (N) stage. Factors associated with prolonged survival were evaluated using Cox proportional hazards mode. Results: One hundred and thirty-one patients who had followed-up over 12 months were enrolled in this study. Kappa coefficient showed weak strength of consistency when comparing the current criteria with histologic analysis (P = 0.0289, Kappa = 0.34, 95% CI 0.05-0.63). However, histologic evaluation resulted in perfect agreement with the mutational method (P < 0.0001, Kappa = 0.85, 95% CI 0.69-1.00). Controlling by N0 stage, patients diagnosed with multiple primary NSCLC showed better relapse-free survival (RFS) than those with intra-pulmonary metastases categorized either by the Martini-Melamed criteria or by histologic-mutational methods (both P < 0001). However, at N+ stage, patients stratified by the Martini-Melamed criteria showed no difference in survival (P = 0.517), but those defined by the histologic-mutational methods still maintained superior survival compared with the Control group (P = 0.042). On multivariate analysis, only N0 and diagnosed as independent lung lesions by histologic-mutational strategy were significant predictors of better RFS (P = 0.031 and P = 0.001, respectively). Conclusions: The diagnostic strategy based on histologic and genetic methods may be an option for identification of synchronous NSCLC when traditional criteria were not applicable, especially in cases with positive lymphatics. N0 stage and diagnosed as independent pulmonary tumours were associated with better RFS. Disclosure: No significant relationships.

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