食管癌新辅助放化疗联合手术与单纯手术治疗效果的随机对照试验Meta分析

Neoadjuvant chemoradiotherapy combined with operation vs. operation alone for resectable esophageal cancer： Meta-analysis on randomized controlled trials

目的对比食管癌新辅助放化疗（NCRT）联合手术与单纯手术治疗的疗效。方法计算机检索Pubmed和WebofScience等英文数据库中关于新辅助放化疗联合手术治疗与单纯手术治疗食管癌的RCT研究，检索时间限定为1990年1月至2015年12月。采用STATA10．0软件进行分析，比较两种治疗方式的近期疗效（R。切除率、阳性淋巴结比率、术后并发症和病死率）和远期疗效（总体生存率以及局部复发率）。用漏斗图和Egger检验进行发表偏倚分析。结果共12项RCT研究的1872例食管癌患者纳入研究，其中NCRT联合手术组939例，单纯手术组943例。近期疗效的Meta分析结果显示，与单纯手术组相比，NCRT联合手术组的R。切除率高（RR=1．19，95％CI：1．08～1．32，P=0．015），病理阳性淋巴结比率低（RR：0．55，95％CI：0．49—0．63，P=0．000），但术后病死率高（RR=1．63，95％CI：1．09～2．45，P=0．018）。两组术后并发症的差异无统计学意义（RR=1．04，95％CI：0．91—1．18，P=0．558）。长期疗效的Meta分析结果显示，与单纯手术组相比，NCRT联合手术组的局部复发率低（RR=0．50，95％CI：0．39～0．64，P=0．000），术后总生存率更优（刎2=0．75，95％CI：0．66～0．84，P=0．001）。对不同的病理类型患者的总体生存率进行亚组分析显示，鳞癌和腺癌亚组患者NCRT术后的总生存率均高于单纯手术者（分别：HR=0．80，95％CI：0．69～0．93，P：0．003；HR=0．78，95％CI：0．70-0．88，P=0．003）。结论新辅助放化疗能降低食管癌的分期，提高R0切除率，且不增加术后总体并发症的发生率；不论对于鳞癌或腺癌患者，新辅助放化疗均能改善患者总体生存。

Objective To compare the treatment outcomes of neoadjuvant chemoradiotherapy （NCRT） combined with operation and operation alone for esophageal cancer. Methods Randomized controlled trials （RCTs）, comparing the treatment outcomes of NCRT combined with operation to operation alone for esophageal cancer, published from January 1990 to December 2015 were searched from PubMed, Web of Science, and other English-language databases. STATA 10.0 software was used to analyze short-term efficacy （R0 resection rate, positive lymph node ratio, postoperative complications and mortality） and long-term outcomes （overall survival rate and local recurrence rate）. The publication bias was evaluated by funnel plot and Egger test. Results A total of 12 RCTs, including 1 872 esophageal cancer patients, were included in the meta-analysis, with 939 cases in NCRT combined with operation group and 943 cases in operation alone group. Meta-analysis of short-term efficacy showed that, as compared to operation alone group, NCRT combined with operation group had higher R0 resection rate （RR = 1.19, 95%CI： 1.08 to 1.32, P= 0.015）, lower positive lymph node rate （RR = 0.55, 95%CI： 0.49 to 0.63, P=0.001）, but higher postoperative mortality （RR = 1.63, 95%CI： 1.09 to 2.45, P=0.018）. Postoperative complications were similar between the two groups（RR = 1.04, 95%CI： 0.91 to 1.18, P=0.558）. Meta-analysis of long-term outcomes showed that, as compared to operation alone group, NCRT combined with operation group had lower local recurrence rate （RR = 0.50, 95% CI： 0.39 to 0.64, P=0.000）, and higher overall survival rate （HR = 0.75, 95%CI： 0.66 to 0.84, P= 0.001 ）. Subgroup analysis according to pathological types showed that both squamous cell carcinoma and adenocarcinoma patients in NCRT combined with operation group had higher overall survival rates compared to those in operation alone group （HR = 0.80, 95%CI： 0.69 to 0.93, P=0.003; HR = 0.78, 95%CI： 0.70 to 0.88, P=0.003）. Conclusions NCRT can decrease the staging of esophageal cancer, elevate the R0 resection rate, and ameliorate local recurrence without increasing postoperative complications. Meanwhile NCRT can improve overall survival of esophageal cancer patients even with squamous cell carcinoma and adenocarcinoma.