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目的:基于SEER数据库分析手术治疗后T0～4N2M0期肺大细胞神经内分泌癌(pLCNEC)患者的预后。方法:在SEER数据库中检索2000－2019年病理诊断明确为大细胞神经内分泌癌/复合型大细胞神经内分泌癌(8013/3)，且原发部位为肺的病例，共5 450例。最终纳入符合研究条件的T0～4N2M0期pLCNEC患者共600例。根据是否进行手术治疗分为非手术治疗组(386例)和手术治疗组(214例)。为减少人口学和临床特征基线差异对结果的影响，采用倾向评分匹配(PSM)分析对2组患者进行匹配，匹配因素包括性别、年龄、种族、手术、放疗、化疗、分期。比值为1，卡尺值为0.02。共匹配成功181对，其中精确匹配46对，模糊匹配135对。根据PSM后是否进行手术治疗分为手术组(181例)和非手术组(181例)。比较手术治疗组与非手术治疗组、手术组与非手术组患者的基线资料。采用Kaplan-Meier法绘制PSM后患者生存曲线，以及按T分期、放疗情况、化疗情况划分亚组的生存曲线，采用Log-rank检验进行比较。采用多因素Cox回归分析影响pLCNEC患者总生存期(OS)和肿瘤特异生存期(CSS)的因素。结果:非手术治疗组中男197例，女189例，≥71岁的高龄患者较多(45.3%，175/386)，T3～4N2M0期占大多数(58.3%，225/386)，66.1%(255/386)的患者接受了放疗。手术治疗组中男123例，女91例，61～70岁患者较多(40.7%，87/214)，T0～2 N2M0期占大多数(65.4%，140/214)，43.9%(94/214)的患者接受了放疗。2组患者年龄、种族、放疗、T分期比较差异均有统计学意义(均 P<0.05)，性别和化疗比较差异均无统计学意义(均 P>0.05)。PSM后，非手术组和手术组患者的基线特征比较差异均无统计学意义(均 P>0.05)。PSM后，手术组中位OS为21个月(95% CI：16～26个月)，非手术组中位OS为13个月(95% CI：10～16个月)，手术组患者的生存状态优于非手术组患者的生存状态( χ2＝11.14， P<0.001)。多因素Cox回归分析显示男性、年龄≥71岁、黑人、T3～4期是影响T0～4N2M0期pLCNEC患者OS的独立危险因素，手术、化疗是影响T0～4N2M0期pLCNEC患者OS的独立保护因素；男性、年龄≥71岁、T3～4期是影响T0～4N2M0期pLCNEC患者CSS的独立危险因素，手术、化疗是影响T0～4N2M0期pLCNEC患者CSS的独立保护因素。T0～2期亚组中手术患者的生存状态优于非手术患者( χ2＝9.36， P＝0.002)，T3～4期亚组中手术与非手术患者的生存状态相近( χ2＝2.75， P＝0.097)。行放疗亚组中，手术与非手术患者的生存状态相近( χ2＝0.98， P＝0.323)；未行放疗亚组中，手术患者的生存状态优于非手术患者( χ2＝14.51， P<0.001)。行化疗亚组中，手术患者的生存状态优于非手术患者( χ2＝11.44， P<0.001)，未行化疗亚组中，手术与非手术患者的生存状态相近( χ2＝1.75， P＝0.186)。 结论:对于T0～4N2M0期，尤其是T0～2N2M0期的pLCNEC患者，手术可以降低死亡风险，并且手术联合化疗较单纯化疗预后好。

Objective:To analyze the prognosis of patients with T0-4N2M0 stage pulmonary large cell neuroendocrine carcinomas (pLCNECs) who underwent surgical treatment by searching data in the Surveillance, Epidemiology, and End Results (SEER) database.Methods:Clinical data of 5, 450 patients with pathologically confirmed large cell neuroendocrine carcinomas/compound large cell neuroendocrine carcinomas (8013/3) with the primary site of the lung were extracted from the SEER database between 2000 and 2019.A total of 600 eligible patients with T0-4N2M0 stage pLCNEC were finally included.They were assigned into the non-surgical group (386 cases) and surgical group (214 cases) based on the performance of surgery or not.In order to reduce the impact of the baseline differences in demographic and clinical characteristics on the results, propensity score matching (PSM) analysis was used to match the patients in the two groups, with the matching factors of gender, age, race, surgery, radiotherapy, chemotherapy, and tumor stage.At a PSM ratio of 1∶1, the match tolerance was set at 0.02.A total of 181 pairs were successfully matched, including 46 exact matches and 135 fuzzy matches.After matching, patients were assigned into the surgery group (181 cases) and the non-surgery group (181 cases) based on the performance of surgery or not.The baseline data of surgical group and non-surgical group, surgery group and non-surgery group were compared.The survival curves of the patients in the two groups after PSM, and those subdivided by T staging, radiotherapy, and chemotherapy were drawn using the Kaplan-Meier method, followed by the log-rank test for pairwise comparations.Multivariate Cox regression analysis was used to analyze the influencing factors for overall survival (OS) and cancer specific survival (CSS) of pLCNEC patients.Results:In the non-surgical group, there were 197 males and 189 females.Most of them in the non-surgical group was ≥71 years (45.3%, 175/386), and the majority was in T3-4N2M0 stage (58.3%, 225/386).66.1% (255/386) patients received radiotherapy.In the surgical group, there were 123 males and 91 females, with the majority of patients aged 61-70 years (40.7%, 87/214), in T0-2N2M0 stage (65.4%, 140/214), and 43.9% (94/214) patients received radiotherapy.There were significant differences in age, race, radiotherapy and T stage between groups (all P<0.05), while there were no significant differences in gender and chemotherapy (all P>0.05).After PSM, there were no significant differences in baseline characteristics between the non-surgery group and the surgery group (all P>0.05).After PSM, the median OS was 21 months (95% CI: 16-26 months) in the surgery group and 13 months (95% CI: 10-16 months) in the non-surgery group.The survival status of the surgery group was significantly better than that of the non-surgery group ( χ2=11.14, P<0.001).The multivariate Cox regression analysis showed that male, age ≥ 71 years, black people, and T3-4 stage were independent risk factors for OS in stage T0-4N2M0 pLCNEC patients, while surgery and chemotherapy were independent protective factors.Male, age ≥ 71 years and T3-4 stage were independent risk factors for CSS in stage T0-4N2M0 pLCNEC patients, while surgery and chemotherapy were independent protective factors.In the subgroup of T0-2 stage, the survival status of the surgical patients was significantly better than that of the non-surgical patients ( χ2=9.36, P=0.002).In the subgroup of T3-4 stage, the survival status of the surgical and non-surgical patients was similar ( χ2=2.75, P=0.097).In the radiotherapy subgroup, the survival status of the surgical and non-surgical patients was similar ( χ2=0.98, P=0.323).In the patients who did not receive radiotherapy, the survival status of surgical patients was significantly better than that of non-surgical patients ( χ2=14.51, P<0.001).In the patients who received chemotherapy, the survival status of surgical patients was significantly better than that of non-surgical patients ( χ2=11.43, P<0.001), while the survival status of surgical and non-surgical patients was similar in the patients who did not receive chemotherapy ( χ2=1.75, P=0.186). Conclusions:For pLCNEC patients in T0-4N2M0 stage, especially those in T0-2N2M0 stage, surgery can significantly reduce the risk of death.Furthermore, the prognosis of patients treated with surgery combined chemotherapy is better than those with surgery alone.