Outcomes for localized treatment of large cell neuroendocrine carcinoma of the lung in the United States

BACKGROUND: Treatment paradigms for large cell neuroendocrine carcinoma (LCNEC) of the lung are based largely upon small retrospective studies and smaller prospective trials. It is unclear if these tumors behave like non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Data are lacking with regard to the role of radiotherapy (RT). U. S. guidelines recommend that LCNEC be treated as a NSCLC. We sought to perform a cross-sectional study of LCNEC cases to understand treatment paradigms and outcomes in this disease. METHODS: The Surveillance, Epidemiology and End Results database was queried for cases of stage I–III pulmonary LCNEC diagnosed 2004–2013. Treatment groups were defined as no surgery, RT alone, surgery alone, and surgery + RT. The Cox-proportional hazards regression model was used to compare overall survival and cause-specific survival (OS/CSS), stratified by AJCC 6th Staging. Factors that were significant on univariable analysis were included in multivariable analysis. RESULTS: We identified 1,523 cases of LCNEC, with 748, 177, and 598 cases of stage I, II, and III disease, respectively. In stage I and II disease, RT was associated with improved survival for non-surgical patients, but not for those who underwent surgery. In stage I disease, the adjusted hazard ratios for OS for RT alone, surgery, and surgery + RT were 0.39, 0.21, and 0.22, respectively (P<0.001). In stage II disease, the adjusted hazard ratios for RT alone, surgery, and surgery + RT were 0.51 (P=0.15), 0.39 (P=0.004), and 0.38 (P=0.01), respectively. For patients with stage III disease, RT was associated with improved survival in surgical and non-surgical patients. The adjusted hazard ratios for RT alone, surgery, and surgery + RT were 0.49, 0.43, and 0.36, respectively (P<0.001). CONCLUSIONS: Our findings indicate that non-metastatic LCNEC may be treated as a NSCLC with respect to RT. Prospective studies are necessary to increase our understanding of optimal treatment regimens.