结直肠癌同时性肝转移新辅助化疗后手术对比直接手术患者的生存疗效

Comparative study on prognosis of neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery in patients with synchronous colorectal liver metastasis

目的对比结直肠癌同时性肝转移行新辅助化疗后手术与直接手术患者的生存疗效。方法本研究采用回顾性队列研究方法,纳入在2008年1月至2018年12月期间,北京大学肿瘤医院肝胆胰外一科收治的282例初始评估为技术上可切除的结直肠同时性肝转移患者。以肝转移术前是否接受过新辅助化疗,分为新辅助化疗组(244例)和直接手术组(38例),比较两组的总生存时间(OS)和无进展生存时间(PFS)。采用倾向性评分校正后进行Cox多因素生存分析,校正的因素包括:性别、年龄、原发肿瘤部位、原发肿瘤T分期、临床风险评分(CRS)、RAS状态、辅助化疗有无、切缘状态。结果244例新辅助化疗组患者术前完成4(1~15)个周期的化疗,其中207例患者一线选择奥沙利铂为主的化疗方案,37例患者一线选择伊利替康为主的化疗方案,90例患者一线联合了靶向治疗。全组患者中位随访时间为30(5~134)个月,失访率1%。未校正前,新辅助化疗组1、3年OS分别为95.1%和66.4%,直接手术组1、3年OS分别为94.7%和51.5%,差异有统计学意义(P=0.026);新辅助化疗组1、3年PFS分别为51.0%和23.4%,直接手术组1、3年PFS分别为39.5%和11.5%,差异有统计学意义(P=0.039)。经倾向性评分校正后,Cox多因素分析显示,新辅助化疗是PFS的独立保护因素(HR=0.664,95%CI:0.449~0.982,P=0.040),但不是OS的独立保护因素(HR=0.651,95%CI:0.393~1.079,P=0.096)。亚组分析显示:新辅助一线化疗有效组(194例,包括完全缓解、部分缓解及缩小但未达到部分缓解)的1、3年OS分别为96.9%和67.1%,优于直接手术组(94.7%和51.5%),经倾向性评分校正后差异有统计学意义(P=0.026);而新辅助一线化疗无效组(50例,包括肿瘤进展或增大)的1、3年OS分别为90.0%和63.3%,与直接手术组(94.7%和51.5%)相比,经倾向性评分校正后差异无统计学意义(P=0.310)。结论对于可切除的结直肠癌同时性肝转移患者,新辅助化疗后行肝切除手术相对于直接手术可使患者获得更长的疾病控制时间,虽然整体OS获益不明显,但新辅助一线化疗有效患者的OS优于直接手术者。

Objective To compare the survival outcome in patients with synchronous colorectal cancer liver metastasis receiving neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery strategies.Methods A retrospective cohort study was carried out.Data of patients undergoing surgery at the Department of Hepatopancreatobiliary Surgery Unit I of Peking University Cancer Hospital from January 2008 to December 2018 for initially resectable synchronous colorectal liver metastasis were retrospectively collected.A total of 282 cases were enrolled,including 244 in the neoadjuvant chemotherapy group,38 in the upfront surgery first group.The overall survival(OS)and progression-free survival(PFS)of the two groups were compared.A propensity score risk adjustment was used to eliminate potential bias between groups,and the covariates including sex,age,location of primary tumor,T stage,clinical risk score(CRS),RAS gene status,adjuvant chemotherapy,and resection margin status were included for adjustment.Results In the neoadjuvant chemotherapy group,244 cases received 4(1-15)cycles of chemotherapy before hepatic resection,among whom 207 cases received oxaliplatin-based regimens,37 cases received irinotecan-based regimens,and 90 cases received combined targeted agents in the first line treatment.The median follow-up time was 30(5-134)months,and loss of follow-up was 1%.Before adjustment,Kaplan-Meier survival analysis showed that the 1-year and 3-year OS rates in the neoadjuvant chemotherapy group(95.1%and 66.4%)were better than those in the upfront surgery first group(94.7%and 51.5%,P=0.026);1-year and 3-year PFS rates in neoadjuvant chemotherapy group(51.0%and 23.4%)were also better than those in surgery first group(39.5%and 11.5%,P=0.039).After propensity score risk adjustment,Cox multivariate analysis indicated that neoadjuvant chemotherapy was an independent protective factor of PFS(HR=0.664,95%CI:0.449-0.982,P=0.040),however,neoadjuvant chemotherapy was not an independent protective factor of OS(HR=0.651,95%CI:0.393-1.079,P=0.096).Subgroup analysis showed that the 1-year and 3-year OS rates in the patients with response to the first line treatment(194,including complete remission,partial remission and reduction but not partial remission)(96.9%and 67.1%)were better than those in the upfront surgery group(94.7%and 51.5%,P=0.026)after adjustment.However,the 1-year and 3-year OS rates in the patients without response to the first line treatment(50,including tumor progression or enlargement)were 90.0%and 63.3%,respectively,which were not significantly different with 94.7%and 51.5%in the upfront surgery group(P=0.310)after adjustment.Conclusions For patients with resectable synchronous colorectal cancer liver metastasis,liver resection after neoadjuvant chemotherapy can provide longer PFS than upfront surgery.Although the whole OS benefit is not significant,patients with effective neoadjuvant first-line chemotherapy have better OS than those undergoing upfront surgery.