新辅助放化疗联合全盆腔脏器切除术治疗原发性T4b期直肠癌的疗效分析

Efficacy analysis of neoadjuvant chemoradiotherapy combined with total pelvic exenteration in the treatment of primary T4b rectal cancer

目的探讨新辅助放化疗联合全盆腔脏器切除术在原发性T4b期直肠癌治疗中的价值。方法采用回顾性队列研究方法,分析北京大学第一医院于2008年1月至2015年12月期间收治并行全盆腔脏器切除术(TPE)的原发性T4b期直肠癌患者临床病理资料。纳入标准为:术前临床分期(cTNM)分期为cT4b期的原发性直肠癌,且仅向前壁侵犯;肿瘤下缘距肛缘10cm以内;接受TPE术,且病理证实为R0切除。排除复发性直肠癌、远处转移者以及合并非直肠肿瘤而行TPE者。按是否行新辅助放化疗(nCRT)分为nCRT组(13例)和非nCRT组(18例)。nCRT组接受术前长程放疗(总剂量50Gy,分割25次),同步口服卡培他滨,在新辅助放化疗结束6~8周后行TPE;非nCRT组则直接手术治疗。分析比较两组患者术中、术后及病理情况、以及局部复发情况,采用Kaplan-Meier法绘制生存曲线并比较两组生存情况。结果共纳入31例患者,nCRT组13例,非nCRT组18例,两组患者年龄、病程时长、术前基础疾病、体质指数、吸烟比例以及肿瘤距肛缘的距离等基线资料的比较,差异无统计学意义(均P>0.05),具有可比性。nCRT组与非nCRT组患者保肛比例分别为30.8%(4/13)和38.9%(7/18)(P=0.468),中位术中出血量分别为1000ml和800ml(P=0.644),手术时间分别为(531.7±137.2)min和(498.0±90.1)min(P=0.703),术后中位住院时间分别为18d和14d(P=0.400),术后30d内并发症发生率分别为23.1%(3/13)和38.9%(7/18)(P=0.452),术后腹腔脓肿发生率分别为15.4(2/13)和0(P=0.168),术后二次手术比率分别为7.7%(1/13)和11.1%(2/18)(P=1.000),差异均无统计学意义。全组术后病理ypT4b比例为58.1%(18/31),其中nCRT组53.8%(7/13),非nCRT组61.1%(11/18),两组间差异无统计学意义(P=0.691)。nCRT组淋巴结清扫数目为(13.5±5.9)枚,明显少于非nCRT组(23.0±11.8)枚(P=0.013)。nCRT组中无病理完全缓解(ypCR)病例,13例患者肿瘤消退分级(TRG)2、3、4、5级分别为1例(7.7%)、6例(46.2%)、5例(38.5%)和1例(7.7%)。全组中位随访时间33(2~115)个月,随访率93.5%(29/31),nCRT组与非nCRT组各失访1例。全组3年无病生存率为43.5%,nCRT和非nCRT组分别为43.6%和43.3%,两组差异无统计学意义(P=0.833);全组3年总体生存率为51.1%,nCRT和非nCRT组分别为45.7%和54.7%,两组间差异亦无统计学意义(P=0.653)。nCRT和非nCRT组局部复发率分别为8.3%(1/12)和5.9%(1/17),远处转移率分别为50.0(6/12)和41.2%(7/17),两组比较,差异均无统计学意义(分别P=1.000和P=0.865)。结论对于通过联合脏器切除可达到R0切除的原发性T4b期直肠癌,新辅助放化疗并未体现出肿瘤降期、降低局部复发率、改善生存率的优势,反而有增加术后并发症的趋势。

Objective To investigate the value of neoadjuvant chemoradiotherapy(nCRT)combined with total pelvic exenteration(TPE)in the treatment of primary T4b rectal cancer.Methods A retrospective cohort study was conducted to analyze the clinicopathological data of 31 patients with primary T4b rectal cancer who underwent TPE from January 2008 to December 2015 at Peking University First Hospital.Inclusion criteria: preoperative clinical stage(cTNM)was defined as cT4b primary rectal cancer with only front wall Invasion;the lower edge of tumor was within 10 cm from the anal margin;TPE was performed;R0 resection was confirmed by pathology.Patients with recurrent rectal cancer,distant metastasis,and undergoing TPE for non-rectal tumors were excluded.Patients were divided into nCRT group and non-nCRT group according to whether receiving nCRT before surgery.The nCRT group received long course radiotherapy(total dose 50 Gy in 25 daily fractions)with concomitant chemotherapy(Capecitabine),and the surgery was performed 6-8 weeks after the neoadjuvant chemoradiation,while the non-nCRT group received surgery directly.The intraoperative,postoperative and pathological conditions and local recurrence were compared between the two groups.The survival curves were drawn by Kaplan-Meier method and the survival of two groups were compared.Results A total of 31 patients were enrolled,including 13 patients in the nCRT group and 18 patients in the non-nCRT group.The baseline data,such as age,duration of disease,preoperative basic disease,body mass index,smoking rate,and tumor distance from the anal margin,were not significantly different between the two groups(all P>0.05).In the nCRT group and non-nCRT group respectively,the ratio of anal preservation was 30.8%(4/13)and 38.9%(7/18)(P=0.468),the median intraoperative blood loss was 1 000 ml and 800 ml(P=0.644),the operation time was(531.7±137.2)minutes and(498.0±90.1)minutes(P=0.703),the median hospital stay was 18 days and 14 days(P=0.400),the morbidity of complications within 30 days after surgery was 23.1%(3/13)and 38.9%(7/18)(P=0.452),the incidence of postoperative abdominal abscess was 15.4%(2/13)and 0(P=0.168),the proportion of secondary surgery was 7.7%(1/13)and 11.1%(2/18)(P=1.000),whose differences were not significantly different.The proportion of postoperative pathological pT4b in whole group was 58.1%(18/31),including 53.8%(7/13)in nCRT group and 61.1%(11/18)in non-nCRT group,which was not significantly different between the two groups(P=0.691).The number of harvested lymph node in nCRT group was 13.5±5.9,which was significantly less than 23.0±11.8 in non-nCRT group(P=0.013).There was no pathological complete remission(ypCR)case in nCRT group,and among 13 patients,tumor regression grade(TRG)of 2,3,4,and 5 was in 1 case(7.7%),6 cases(46.2%),5 cases(38.5%),and 1 case(7.7%),respectively.The median follow-up time was 33(2 to 115)months,and the follow-up rate was 93.5%(29/31).One case was lost in both the nCRT group and non-nCRT group.The 3-year disease-free survival rate was 43.5% in pooled data,and was 43.6% and 43.3% in nCRT group and non-CRT group respectively without significant difference(P=0.833).The 3-year overall survival rate was 51.1% in pooled data,and was 45.7% and 54.7% in nCRT group and non-nCRT group respectively without significant difference(P=0.653).The local recurrence rate of nCRT and non-nCRT groups was 8.3%(1/12)and 5.9%(1/17)respectively,and the distant metastasis rate was 50.0%(6/12)and 41.2%(7/17)respectively,whose differences were not statistically significant as well(P=1.000 and P=0.865,respectively).Conclusion For primary T4b rectal cancer which can achieve R0 resection through total pelvic exenteration,neoadjuvant chemoradiotherapy has not been demonstrated any advantage in tumor regression,reducing local recurrence,or improving survival,and may increase postoperative complications.