Lai Xu1, Xiangqian Su2, Zirui He3, Chenghai Zhang2, Junyang Lu1, Guannan Zhang1, Yueming Sun4, Xiaohui Du5, Pan Chi6, Ziqiang Wang7, Ming Zhong8, Aiwen Wu9, Anlong Zhu10, Fei Li11, Jianmin Xu12, Liang Kang13, Jian Suo14, Haijun Deng15, Yingjiang Ye16, Kefeng Ding17, Tao Xu18, Zhongtao Zhang19, Minhua Zheng3, Yi Xiao20. 1. Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China. 2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing, China. 3. Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 4. Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 5. Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing, China. 6. Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fujian, China. 7. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China. 8. Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 9. Department of Unit III & Ostomy Service, Gastrointestinal Cancer Centre, Peking University Cancer Hospital and Institute, Beijing, China. 10. Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. 11. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China. 12. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. 13. Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 14. Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China. 15. Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. 16. Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China. 17. Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention (Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 18. Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China; School of Basic Medicine, Peking Union Medical College, Beijing, China. 19. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Centre for Digestive Diseases, Beijing, China. 20. Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China. Electronic address: xiaoy@pumch.cn.
Abstract
BACKGROUND: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial. METHODS: This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18-75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes-intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only-are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing. FINDINGS:Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, -2·2% [95% CI -7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I-II complications were similar between groups (91 [18%] vs 92 [18%], difference, -0·0% [95% CI -4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III-IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], -2·2% [-4·1 to -0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymphnode biopsy in the CME group; no patient had isolated metastases to central lymph nodes. INTERPRETATION: Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons. FUNDING: The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences.
RCT Entities:
BACKGROUND: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial. METHODS: This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18-75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes-intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only-are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing. FINDINGS: Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, -2·2% [95% CI -7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I-II complications were similar between groups (91 [18%] vs 92 [18%], difference, -0·0% [95% CI -4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III-IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], -2·2% [-4·1 to -0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes. INTERPRETATION: Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons. FUNDING: The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences.