放疗联合手术治疗局部进展期直肠黏液腺癌的疗效分析:一项基于SEER数据库的回顾性研究

Efficacy analysis of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma: a retrospective study based on data of Surveillance,Epidemiology,and End results population

目的探讨放疗联合手术治疗局部进展期直肠黏液腺癌的临床疗效。方法通过检索美国SEER数据库中1992—2013年术后病理明确诊断为局部进展期直肠黏液腺癌[T3~4和(或)N+]患者的临床资料;排除仅行局部切除、肿瘤活检或联合脏器切除者以及随访信息不完整者。将所有纳入患者根据不同的治疗策略分为3个亚组,包括单纯手术组、术前放疗联合手术组及手术联合术后放疗组。提取的数据包括患者基本资料、肿瘤基本资料、治疗情况以及随访结果。计数资料的比较采用χ^2检验。采用Kaplan-Meier绘制生存曲线和计算生存率,生存分析比较采用Log-rank检验。采用R语言2.8.1对患者通过倾向性评分进行1∶1匹配,匹配变量包括性别、确诊年龄、确诊年份、人种、组织分化程度、TNM分期、浸润深度,使亚组间基线资料具有可比性。采用Cox比例风险模型进行预后因素的多因素分析。结果共2149例局部进展期直肠黏液腺癌患者纳入研究,其中男性1255例(58.4%),女性894(41.6%)。单纯手术组有706例(32.9%),术前放疗联合手术组有772例(35.9%),手术联合术后放疗组671例(31.2%)。单纯手术组、术前放疗联合手术组和手术联合术后放疗组间的中位生存时间分别为39、85和74个月,5年总体生存率分别为38.7%、56.5%和55.2%;中位肿瘤特异性生存时间分别为86、127及111个月,5年肿瘤特异性生存率分别为53.7%、62.2%和60.7%;3组间比较,单纯手术组的5年总体生存率和5年肿瘤特异性生存率均明显低于术前放疗联合手术组和手术联合术后放疗组(均P<0.001);术前放疗联合手术组与手术联合术后放疗组的5年总体生存率和肿瘤特异性生存率差异均无统计学意义(分别P=0.166和P=0.392)。经倾向性评分对单纯手术组和术前放疗联合手术组患者的基线资料进行校正后,共750例患者匹配成功,单纯手术组(375例)和术前放疗联合手术组(375例)的5年总体生存率分别为40.1%比54.5%(P<0.001),5年肿瘤特异性生存率分别为54.3%比63.3%(P=0.023),差异均具有统计学意义;经倾向性评分对单纯手术组和手术联合术后放疗组的基线资料进行校正后,共806例患者匹配成功,单纯手术组(403例)和手术联合术后放疗组(403例)的5年总体生存率分别为37.4%比54.7%(P<0.001),5年肿瘤特异性生存率分别为51.6%比61.0%(P=0.031),差异也具有统计学意义;而经倾向性评分对术前放疗联合手术组和手术联合术后放疗组的基线资料进行校正后,共726例患者匹配成功,术前放疗联合手术组(363例)和手术联合术后放疗组(363例)的5年总体生存率分别为51.7%比55.5%(P=0.789),5年肿瘤特异性生存率分别为57.7%比60.5%(P=0.484),差异均无统计学意义。Cox多因素分析显示,放疗(HR=0.845,95%CI:0.790~0.903,P=0.001)是影响局部进展期直肠黏液腺癌总体生存的独立预后因素;放疗(HR=0.907,95%CI:0.835~0.985,P=0.021)亦是影响局部进展期直肠黏液腺癌患者肿瘤特异性生存的独立预后因素。结论与单纯手术相比,术前与术后联合放疗均能使局部进展期直肠黏液腺癌患者远期生存获益。

Objective To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma.Methods Clinical data of patients with locally advanced rectal mucinous adenocarcinoma(T3-4 and/or N+)diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance,Epidemiology,and End Results(SEER)database.Patients with local excision only,tumor biopsy or combined organ excision and incomplete follow-up information were excluded.All the enrolled patients were divided into three groups according to different treatments,including surgery alone(SA)group,preoperative radiotherapy combined with surgery(RT+S)group and surgery combined with postoperative radiotherapy(S+RT)group.The extracted data included basic data of patients and tumor,treatment status,and follow-up results.The χ^2 test was used to compare the count data.Kaplan-Meier method was used to draw the survival curve and calculate the survival rate.The survival was analyzed and compared by Log-rank test.The R language 2.8.1 was used to match the patients as 1∶1 pairing through the propensity score matching(PSM).The matching variables included gender,age at diagnosis,year at diagnosis,ethnicity,degree of tissue differentiation,TNM stage,depth of invasion,making the baseline data of subgroups comparable.The Cox proportional hazard model was used for multivariate analysis of prognostic factors.Results A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study,including 1 255 males(58.4%)and 894 females(41.6%).There were 706 patients(32.9%)in the SA group,772 patients(35.9%)in the RT+S group and 671 patients(31.2%)in the S+RT group.In SA,RT+S and S+RT groups,the median overall survival time was 39,85,and 74 months respectively;the 5-year overall survival(OS)rate was 38.7%,56.5%,and 55.2% respectively;the median cancer-specific survival(CSS)time was 86,127,and 111 months respectively,and the 5-year CSS rate was 53.7%,62.2% and 60.7% respectively.In comparison among the 3 groups,the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group(all P<0.001);the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different(P=0.166 and 0.392,respectively).After the baseline data of subgroups were corrected through PSM,the 5-year OS rate and CSS rate in the SA group(n=375)were significantly lower than those in the RT+S group(n=375)(OS: 40.1% vs.54.5%,P<0.001;CSS: 54.3% vs.63.3%,P=0.023).The 5-year OS rate and CSS rate in the SA group(n=403)were also lower than those in the S+RT group(n=403)(OS: 37.4% vs.54.7%,P<0.001;CSS: 51.6% vs.61.0%,P=0.031).The 5-year OS rate and CSS rate between RT+S group(n=363)and S+RT group(n=363)were not significantly different(OS: 51.7% vs.55.5%,P=0.789;CSS: 57.7% vs.60.5%,P=0.484).Cox multivariate analysis showed that radiotherapy(HR=0.845,95%CI: 0.790 to 0.903,P=0.001)was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma;radiotherapy(HR=0.907,95% CI: 0.835 to 0.985,P=0.021)was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma.Conclusion As compared with surgery alone,surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.