Optimal Surgery Type and Adjuvant Therapy for T1N0M0 Lung Large Cell Neuroendocrine Carcinoma

Abstract

BackgroundThe appropriate treatment strategy for T1N0M0 lung large cell neuroendocrine carcinoma (LCNEC) was not well illustrated. We evaluated the efficacy of different surgery types and adjuvant therapy on patients with T1N0M0 LCNEC.MethodsPatients diagnosed T1N0M0 LCNEC from 2004 to 2016 were identified in the surveillance, epidemiology, and end results (SEER) database. Clinical characteristics, treatment and survival data were collected. The efficacy of surgery type and adjuvant therapy stratified by tumor size was assessed. Overall survival(OS) was evaluated by the Kaplan-Meier method, and relevant survival variables were identified by the Cox proportional hazard model.ResultsFrom 2004 to 2016, 425 patients were included in this study, 253 (59.5%) patients received lobectomy, and 236 (55.5%) patients had 4 or more lymph nodes removed. Patients received lobectomy had better survival than those received sublobar resection(P=0.000). No matter tumor size less than 2 cm or 2 to 3 cm, lobectomy was significantly prolonged survival. Compared with no lymph nodes removed, lymph nodes dissection was associated with more remarkable OS(P<0.000). 4 or more regional lymph nodes dissection predicted better OS compared with 1 to 3 regional lymph nodes dissection(P=0.014). After surgery, adjuvant chemotherapy did not contribute to extended survival in patients with tumor less than 2 cm(P=0.658), and possibly for tumor 2 to 3 cm(P=0.082). Multivariate analysis showed that age and lobectomy were independent prognostic factors(P=0.000).ConclusionOur results suggest that lobectomy and lymph nodes dissection were associated with significantly better survival. Extensive regional lymph node dissection(4 or more) was more effective in prolonging survival than 1 to 3 lymph nodes dissection. Adjuvant chemotherapy was not associated with extended survival for tumor less than 2 cm, and possibly for tumor 2 to 3 cm.

Recurrence-Free Survival in Early and Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung after Complete Tumor Resection

“…In keeping with previous studies, we confirmed that LCNECs are often associated with the male sex (67% older age, median age 64 years) and smoker status (87%) [ 6 , 7 , 19 , 21 , 24 ]. However, in some other studies, a prevalence of females or non-smokers was reported [ 9 , 14 , 24 ]. Most patients reported non-specific symptoms, such as fever or chest and back pain, whereas cough and hemoptysis were only described in a few patients (18%), in line with previous data [ 1 , 32 ].…”

“…LCNEC is a rare subtype of lung cancer with a high relapse rate [ 31 ]. Due to its low frequency, data related to early-stage LCNEC derived only from a relatively low number of studies [ 6 , 7 , 9 , 14 , 15 , 16 , 19 ], which included heterogeneous cohorts of patients having also patients with advanced diseases or who did not undergo tumor resection, or with a diagnosis of combined-LCNEC at histopathological analysis. Studies including only early and locally advanced LCNEC after complete resection of the tumor are very few [ 21 , 22 , 23 , 24 ] and focused mostly on overall survival ( Table 1 ).…”

“…In patients with early-stage SCLC, surgery may be considered in patients with clinical stages I and II (cT1–2N0) in the context of a multimodal treatment concept and following a multidisciplinary board decision [III, B] [ 13 ]. Two large population-based studies in LCNEC evaluating the Surveillance, Epidemiology, and End Results (SEER) database showed that surgical resection of the tumor was significantly associated with a better OS compared to not resected tumor, independently to tumor stage [ 3 , 14 ]. However, in addition, the early-stage disease rapidly recurs after the tumor resection, with a 5-year recurrence-free survival (RFS) of 35–43% [ 8 , 9 , 15 , 16 ].…”

“…A small single-arm prospective trial demonstrated that adjuvant cisplatin-etoposide chemotherapy was associated with a significant OS improvement compared to historical data of patients treated with surgery alone [ 20 ]. However, some studies failed to find a clinical improvement in patients treated with adjuvant chemotherapy and/or radiotherapy [ 9 , 14 , 16 , 21 ].…”

“…Although the 5-year rate of recurrence in LCNEC (also at early-stage) is high and similar or close to the 5-year OS rate [ 8 , 9 , 10 , 16 ], most studies, including large national databases [ 3 , 6 , 14 , 19 ], focused as the primary endpoint to OS. Moreover, data on RFS in early-stage LCNEC are lacking [ 8 , 9 , 16 , 20 ].…”