参与外科临床试验对右半结肠癌患者手术安全性及预后的影响

Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer

目的探索参与外科临床研究对右半结肠癌患者术后安全性及预后的影响。方法采用回顾性队列研究的方法。以北京协和医院结直肠专业组腹腔镜完整结肠系膜切除术(CME)对比D2根治切除术治疗右半结肠癌的随机对照研究(RELARC研究)为例,选择2016年1月至2019年12月期间年龄18~75岁、活检病理提示结肠腺癌、肿瘤位于盲肠和横结肠右侧1/3之间、胸腹盆增强CT提示肿瘤分期为T2~4N0M0或TanyN+M0而接受根治性手术治疗患者的临床资料,排除合并多原发结直肠癌、术前评估肿瘤分期为T1N0期或中央淋巴结肿大、肿瘤累及周围器官需行联合器官切除术、明确远处转移或无法行R0切除术、近5年内有任何其他恶性肿瘤病史、合并肠梗阻或肠穿孔及消化道出血等需要急诊手术者以及术前评估不适合腹腔镜手术者。将其中参与RELARC研究者作为RELARC组,对满足入组条件、但拒绝参加RELAEC研究的患者纳入对照组。主要观察指标为患者的基线资料、手术和围手术期情况、肿瘤病理特征及辅助治疗情况以及术后随访(包括术后3年内平均复查频率)和生存情况[包括术后3年无病生存率(DFS)和3年总生存率(OS)]并比较RELARC组与对照组间的差异。结果共计290例患者纳入研究,其中RELARC组173例,82例接受CME手术(RELARC⁃CME组),91例接受D2手术(RELARC⁃D2组);对照组117例,72例接受CME手术(CME对照组),45例接受D2手术(D2对照组)。除RELARC⁃CME组超重(体质指数≥24 kg/m^(2))患者比例显著高于CME对照组[67.1%(55/82)比33.3%(24/72),χ^(2)=17.469,P<0.001]外,其余组间基线资料比较,差异均无统计学意义(均P>0.05)。CME两组及D2两组患者在手术时间、术中出血量、中转开腹比例、联合脏器切除、术中输血和术中并发症发生率的比例差异均无统计学意义(均P>0.05)。术后发生Claiven⁃DindoⅡ级以上并发症的比例,RELARC⁃CME组[24.4%(20/82)]高于CME对照组[18.1%(13/72)],但差异无统计学意义(χ^(2)=0.914,P=0.339);RELARC⁃D2组[25.3%(23/91)]与D2对照组[24.4%(11/45)]比较,差异也无统计学意义(χ^(2)=0.011,P=0.916)。RELARC组术后中位随访复查间隔时间明显短于对照组,差异均有统计学意义[RELARC⁃CME组4.5(4.5,4.5)个月比CME对照组7.2(6.0,9.0)个月(Z=−10.608,P<0.001);RELARC⁃D2组4.5(4.5,4.5)个月比D2对照组8.3(6.6,9.0)个月(Z=−10.595,P<0.001)]。RELARC⁃CME组3年DFS(91.5%)和OS(96.3%)高于CME对照组(84.7%和90.3%),RELARC⁃D2组3年DFS(87.9%)和OS(96.7%)也高于D2对照组(81.8%和88.6%),但差异均无统计学意义(均P>0.05);病理分期的亚组分析中,RELARC⁃D2组中pN0期患者3年OS显著优于D2对照组(100%比88.9%,P=0.008),其余亚组间生存率差异均无统计学意义(均P>0.05)。结论参与具有规范的质量控制及严密随访的外科临床研究,能保障患者围手术期的安全,并且可能有助于改善患者的预后。

Objective To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods This retrospective cohort study utilized data from a randomized controlled trial(RELARC study)conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision(CME)was compared with D2 radical resection for the management of right-sided colon cancer.The eligibility criteria were age 18–75 years,biopsy-proven colon adenocarcinoma,tumor located between the cecum and right 1/3 of the transverse colon,enhanced chest,abdomen,and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+M0,and having undergone radical surgical treatment from January 2016 to December 2019.Exclusion factors included multiple primary colorectal cancers,preoperative stage T1N0 or enlarged central lymph nodes,tumor involving surrounding organs requiring their resection,definite distant metastasis or otherwise unable to undergo R0 resection,history of any other malignant tumors within previous 5 years,intestinal obstruction,perforation,or gastrointestinal bleeding requiring emergency surgery,and assessed as unsuitable for laparoscopic surgery.Patients who had participated in the RELARC study were included in the RELARC group,whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group.The main indicators studied were the patient's baseline data,surgery and perioperative conditions,pathological characteristics,adjuvant treatment,and postoperative follow-up(including average frequency of follow-up within the first 3 years)and survival(including 3-year disease-free survival rate(DFS)and 3-year overall survival rate(OS).Differences in these indicators between the RELARC and control groups were compared.Results The study cohort comprised 290 patients,173 in the RELARC group(RELARC-CME group,82;RELARC-D2 group,91)and 117 in the control group(CME control group,72;D2 control group,45).There was a significantly higher proportion of overweight patients(BMI≥24 kg/m^(2))in the RELARC-CME than in the CME control group(67.1%[55/82]vs.33.3%[24/72],χ^(2)=17.469,P<0.001).There were no other statistically significant differences in baseline characteristics(all P>0.05).No significant disparities were found between the CME and D2 groups in terms of operation duration,intraoperative blood loss,rate of conversion to open surgery,combined organ resection,intraoperative blood transfusion,or intraoperative complications(all P>0.05).There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group(24.4%[20/82])than in the CME control group(18.1%[13/72]);however,this difference was not statistically significant(χ^(2)=0.914,P=0.339).Similarly,the difference in this rate did not differ significantly between the RELARC-D2 group(25.3%[23/91])and D2 control group(24.4%[11/45],χ^(2)=0.011,P=0.916).The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups.Specifically,the median duration of follow-up was 4.5(4.5,4.5)months in the RELARC-CME and 7.2(6.0,9.0)months in the CME control group(Z=−10.608,P<0.001).Similarly,the median duration of follow-up was 4.5(4.5,4.5)months in the RELARC-D2 group as opposed to 8.3(6.6,9.0)months in the D2 control group(Z=−10.595,P<0.001).The 3-year DFS rate(91.5%)and OS rate(96.3%)tended to be higher in the RELARC-CME group than in the CME control group(84.7%and 90.3%,respectively).The 3-year DFS rate(87.9%)and OS rate(96.7%)tended to be higher in the RELARC-D2 group than in the D2 control group(81.8%and 88.6%,respectively);however,these differences were not statistically significant(all P>0.05).Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group(100%vs.88.9%,P=0.008).We identified no statistically significant differences in survival rates between the remaining subgroups(all P>0.05).Conclusions A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.