早期非小细胞肺癌完全性切除术5年后的晚期复发

Study of late recurrence in non-small cell lung cancer patients after complete resection

目的探讨非小细胞肺癌（NSCLC）手术5年后无复发患者晚期复发的风险和意义。方法以496例行完全性切除术的Ⅰ期、ⅡA期的非小细胞肺癌患者为研究对象，于术后前2年每3个月至门诊复查1次，2年后每6个月复查1次。包括查体、影像学检查和检查肿瘤标志物，必要时进行病理学检查。5年无复发者336例继续随访3年，并收集相关的临床、病理资料，主要观察终点是肺癌复发，数据收集至2011年1月。采用Kaplan-Meier法估算无复发生存率，Log-rank法进行生存率显著性检验，应用Cox比例风险回归模型进行多因素分析探讨晚期复发与危险因素之间的关系。结果496例患者术后5年109例死于肺癌复发，33例死于其他原因，18例带瘤生存，336例无复发。无复发者继续随访3-36个月，中位27个月。随访期中34例（10．1％）发生晚期复发，局部复发（纵隔淋巴结复发6例、同侧肺复发3例、胸膜播散2例、其他2例）13例（38．2％），远处转移（多器官转移8例、单器官转移13例中对侧肺脏5例、肝脏3例、中枢神经2例、其他3例）21例（61．8％）。单因素分析发现吸烟、癌胚抗原、分化程度、瘤内淋巴管浸润、瘤内血管浸润、胸膜受累和病理分期是影响3年无复发生存率的因素。多因素分析显示瘤内血管浸润和瘤内淋巴管浸润是影响晚期复发的独立危险因素。结论完全性切除术5年后的NSCLC患者仍存在晚期复发风险，尤其是有瘤内血管浸润和淋巴管浸润的患者，对于该类患者术后5年继续随访是有必要和有意义的。

Objective To investigate the risk fators and significance of late recurrence in non-small cell lung cancer （NSCLC） patients who had undergone complete resection and remained recurrence-free for 5 years. Methods 496 individuals diagnosed and surgically treated for Stage Ⅰand Ⅱ A NSCLC were included. We examined patients at 3-month intervals for the first 2 years after surgery and typically at 6-month intervals thereafter on an outpatient basis. The follow-up evaluation included physical examination, imaging examination and tumor markers. Pathological examination had also been performed when nee- ded. Of these, 336 patients remained recurrence-free for 5 years were followed up continuously for 3 years. Clinicopathologie factors were collected including age, sex, smoking history, preoperative serum carcinoembryonic antigen （CEA） level, surgical approach, maximum tumor dimension on resected specimen, histologie type, histologic differentiation, intratumoral lymphatic permeation, intratumoral vascular invasion, pleural invasion and pathologic stage. The primary end event was lung cancer re- currence. The data collection ended in January 2011. Kaplan-Meier method was used for survival rate. Survival difference was evaluated by log-rank test. Multivariate Cox regression was used to test the relationship of recurrence-free probability to vari（ms clinicopathologic factors. Results At 5 years after resection, 109 patients had died of disease and 33 had died of other cau- ses. 18 patients were alive with disease. The remaining 3 -36 patients were alive and recurrence-free for the first 5 years. The median follow-up period of these 5-year recurrence free survivors was 27 months （ range, 3-36 months）. 34 （ 10.1% ） patients developed a late recurrence at 3 years among the 336 patients. Recurrence was locoregional in 13 （38.2%） patients： 6 patients in mediastinal lymph nodes, 3 patients in ipsilateral lung, 2 patients with pleural dissemination and 2 patients in other loca- tions. Recurrence was distant in 21 （61.8%） patients： 8 patients with multiple-organ metastases, 13 patients with single-organ metastasis, and the latter consisted of 5 patients in eontralateral lung, 3 patients in liver, 2 patients in central nervous system and 3 patients in other locations. Smoking history, preopetative serum CEA level, histologic differentiation, intratumoral lym- phatic invasion, intratumoral vascular invasion, pleural invasion and pathologic stage were risk factors for late recurrence in un-ivariate analysis. Multivariate Cox analysis demonstrated that intratumoral vascular invasion and intratumoral lymphatic invasion were independent risk factors for late recurrence. Conclusion NSCLC patients have a significant risk of late recurrence after complete resection 5 years, especially for the patients with intratumoral vascular invasion and intratumoral lymphatic invasion. It is needed and significant for the patients to follow up continuously after 5 years of complete resection.