非小细胞肺癌淋巴结清扫方式的系统评价和Meta分析

Pattern of lymph node dissection in non-small cell lung cancer:A systematic review and meta-analysis

目的对比淋巴结采样(LN-S)和肺叶特异性淋巴结清扫(L-SLD)治疗早期非小细胞肺癌(NSCLC)的临床疗效和安全性。方法计算机检索Pub Med、Medline、EMbase、Web of Science和The Cochrane Library(2017年2期)数据库公开发表的英文文献,搜集系统性纵隔淋巴结清扫(SMLD)与LN-S或L-SLD治疗NSCLC的随机对照试验(RCT)和队列研究(CS),检索时间均为建库至2017年3月。由2位评价员独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用Rev Man 5.3软件进行直接Meta分析,采用ITC软件进行间接Meta分析。结果共纳入文献18篇,包括4篇RCT和14篇CS,共10 714例患者。直接Meta分析结果表明:CS中与SMLD组相比,L-SLD延长了总生存期,但差异无统计学意义[HR=0.99,95%CI(0.78,1.25),P=0.92],LN-S组总生存期缩短,差异有统计学意义[HR=1.43,95%CI(1.17,1.75),P=0.000 4],但在RCT中差异无统计学意义(P=0.35)。CS中无病生存期SMLD组和LN-S组[HR=1.25,95%CI(0.96,1.62),P=0.10]、L-SLD组[HR=1.15,95%CI(0.92,1.43),P=0.23]差异均无统计学意义。在局部复发率和远处转移率方面,与非系统性淋巴结清扫(NSMLD)相比,SMLD在CS和RCT中差异均无统计学意义(CS:P=0.43,P=0.39;RCT:P=0.24,P=0.10);术后并发症在CS[OR=0.79,95%CI(0.58,1.09),P=0.15]和RCT[OR=0.36,95%CI(0.09,1.45),P=0.15]中差异亦无统计学意义。间接Meta分析显示,与LN-S组相比,L-SLD组死亡风险降低了31%[HR=0.69,95%CI(0.51,0.95),P=0.46],复发风险降低了35%[HR=0.65,95%CI(0.65,1.30),P=0.72],但差异无统计学意义。结论对于早期NSCLC,与L-SLD相比SMLD在生存获益方面差异无统计学意义;而LN-S的总生存期短于SMLD。间接Meta分析显示相比LN-S组,L-SLD组降低死亡风险和复发风险,然而两者的预后尚无直接比较的证据支持,仍需要更进一步的前瞻性研究予以验证。

Objective To compare lymph node sampling（LN-S） and lobe-specific lymph node dissection（LSLD） in the clinical efficacy and safety for early-stage non-small cell lung cancer（NSCLC）. Methods Pub Med, Medline,EMbase, Web of Science and The Cochrane Library databases were searched up to March 2017 for English language studies. We collected randomized controlled trials（RCTs） and cohort studies（CS） which used the systematic mediastinal lymph node dissection（SMLD） and LN-S or L-SLD for the treatment of NSCLC. Direct meta-analysis was performed using Rev Man 5.3 software and indirect meta-analysis with ITC software after two researchers screened the literature,extracted the data and evaluated the risk of bias independently. Results A total of 18 articles were included（4 RCTs and14 CS, and 10 714 patients）. Meta-analysis results showed that in the CS, compared with the the SMLD group, overall survival increased in the L-SLD group（HR=0.99, 95%CI 0.78 to 1.25, P=0.92）, and overall survival decreased in the LN-S group with significant difference in CS（HR=1.43, 95%CI 1.17 to 1.75, P=0.000 4）, but was not statistically significant in RCT（P=0.35）. In terms of disease-free survival, there was no significant difference between the SMLD group and the LN-S group（HR=1.25, 95%CI 0.90, 1.62, P=0.10） as well as the L-SLD group（HR=1.15, 95%CI 0.92 to 1.43, P=0.23） in the CS.There was no significant difference in the local recurrence rate or distant metastasis rate between the non-systematic lymph node dissection（NSMLD） and SMLD in CS and RCTs（CS： P=0.43, P=0.39; RCT： P=0.43, P=0.10）. There was no significant difference in the postoperative complications between NSMLD and SMLD in the CS（OR=0.79, 95%CI 0.58 to1.09, P=0.15） and RCTs（OR=0.36, 95%CI 0.09 to 1.45, P=0.15）. Indirect meta-analysis showed that risk of death decreased by 31% and risk of recurrence by 35% in the L-SLD group compared with the LN-S group（HR=0.69, 95% CI 0.51 to 0.95,P=0.46; HR=0.65, 95% CI 0.65 to 1.30, P=0.72）, but the difference was not statistically significant. Conclusion For earlystage NSCLC, L-SLD is not statistically different from SMLD in terms of survival; however, the overall survival of LN-S is lower than that of systematic lymphadenectomy. Indirect meta-analysis shows that L-SLD reduces the risk of death and recurrence risk compared with LN-S. There is no evidence to support both direct comparison of the prognosis of LN-S and L-SLD, therefore further prospective studies are still needed to verify.