T3期胆囊癌手术治疗联合辅助治疗的多中心回顾性研究

Efficacy analysis of surgical combined with postoperative adjuvant therapy for T3 gallbladder carcinoma: a multicenter retrospective study

目的探讨根治性切除后T3期胆囊癌患者行辅助治疗的临床价值。方法回顾性收集2013年1月至2018年12月中国7家医疗机构肝胆中心通过外科治疗的415例T3期胆囊癌患者的临床和病理学资料。男性251例, 女性164例, 年龄(61±11)岁(范围:26~88岁)。根据根治性切除术后是否接受辅助治疗, 将患者分为单纯根治性切除组(A组, n=358)和根治性切除联合术后辅助治疗组(B组, n=57)。采用倾向性评分匹配法对两组患者的一般资料进行1∶1匹配, 卡钳值取0.02。比较匹配前后两组患者临床和病理学特征、总体生存及无病生存情况。采用Cox回归模型进行多因素分析, 并将具有至少一项独立预后因素的患者归类为高危临床病理学亚型, 通过亚组分析探讨具有高危临床病理学亚型患者根治性切除后接受辅助治疗的临床价值。结果匹配后两组患者各有42例, B组胆囊切除术后胆囊癌的发生率和清扫淋巴结数量高于A组(χ^(2)=9.224、2.570, P值均<0.05)。匹配前后两组患者的总体生存率和无病生存率的差异均无统计学意义(P值均>0.05)。单因素和多因素分析结果显示, CA19-9>39 U/ml、神经侵犯、肿瘤位于肝脏侧或双侧、TNM分期为ⅢB~ⅣB期、肿瘤分化程度低是T3期胆囊癌患者总体生存和无病生存的独立不良预后因素(P值均<0.05)。329例(79.3%)患者具有高危临床病理学亚型, 其中根治性切除后接受和未接受辅助治疗患者的中位生存时间分别为17个月和34个月, 3、5年总体生存率分别为40.0%、21.3%和46.0%、46.0%(χ^(2)=4.042, P=0.044);中位无病生存时间分别为9个月和13个月, 3、5年无病生存率分别为23.4%、13.6%和30.2%、18.2%(χ^(2)=0.992, P=0.319)。结论接受根治性手术后再行辅助治疗没有明显提高T3期胆囊癌患者的总体生存和无病生存率, 但可以显著延长具有高危临床病理学亚型的患者的总体生存时间。

Objective To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer(GBC)who have undergone R0 resection.Methods Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged(61±11)years(range:26 to 88 years).Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone(group A,n=358)and the radical resection combined with the postoperative adjuvant therapy group(group B,n=57).The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes.Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes.Results After the matching,there were 42 patients in each of the two groups.The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A(χ^(2)=9.224,2.570,both P<0.05).There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching(all P>0.05).The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location(liver side or bilateral),TNM stageⅢB toⅣB,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer(all P<0.05).Three hundred and twenty-nine patients(79.3%)had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3%and 46.0%,46.0%(χ^(2)=4.042,P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6%and 30.2%,18.2%(χ^(2)=0.992,P=0.319).Conclusions Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer.However,it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.