*Department of Surgery, Tochigi Cancer Center, Tochigi, Japan †JCOG Data Center/Operations Office, National Cancer Center, Tokyo, Japan ‡Colorectal Surgery Division, National Cancer Center Hospital, Tokyo, Japan §Department of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan ¶Department of Surgery, Shizuoka Cancer Center, Shizuoka, Japan ||Department of Surgery, Aichi Cancer Center Hospital, Nagoya, Japan **Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan ††Department of Surgery, Yokohama City University Medical Center, Kanagawa, Japan ‡‡Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan §§Department of Surgery, Kanagawa Cancer Center, Kanagawa, Japan ¶¶Department of Surgery, Kyoto Medical Center, Kyoto, Japan ||||Department of Surgery, Ishikawa Prefectural Central Hospital, Ishikawa, Japan ***Department of Surgery, Tokyo Medical University Hospital, Tokyo, Japan †††Department of Surgery, Suita Municipal Hospital, Osaka, Japan ‡‡‡Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan §§§Department of Gastroenterological Surgery, Chiba Cancer Center Hospital, Chiba, Japan ¶¶¶Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan ||||||Hospital of the Imperial Household, Tokyo, Japan ****Japanese Red Cross Medical Center, Tokyo, Japan.
Ann Surg. 2017 Aug;266(2):201-207. doi: 10.1097/SLA.0000000000002212.
The aim of the study was to confirm the noninferiority of mesorectal excision (ME) alone to ME with lateral lymph node dissection (LLND) in terms of efficacy.
Lateral pelvic lymph node metastasis is occasionally found in clinical stage II or III lower rectal cancer, and ME with LLND is the standard procedure in Japan. ME alone, however, is the international standard surgical procedure for rectal cancer.
Eligibility criteria included histologically proven rectal cancer at clinical stage II/III; main lesion located in the rectum, with the lower margin below the peritoneal reflection; no lateral pelvic lymph node enlargement; Peformance Status of 0 or 1; and age 20 to 75 years. Patients were intraoperatively allocated to undergo ME with LLND or ME alone in a randomized manner. The primary endpoint was relapse-free survival, with a noninferiority margin for the hazard ratio of 1.34. Secondary endpoints included overall survival and local-recurrence-free survival. Analysis was by intention to treat.
In total, 701 patients were randomized to the ME with LLND (n = 351) and ME alone (n = 350) groups. The 5-year relapse-free survival in the ME with LLND and ME alone groups were 73.4% and 73.3%, respectively (hazard ratio: 1.07, 90.9% confidence interval 0.84-1.36), with a 1-sided P value for noninferiority of 0.0547. The 5-year overall survival, and 5-year local-recurrence-free survival in the ME with LLND and ME alone groups were 92.6% and 90.2%, and 87.7% and 82.4%, respectively. The numbers of patients with local recurrence were 26 (7.4%) and 44 (12.6%) in the ME with LLND and ME alone groups, respectively (P = 0.024).
The noninferiority of ME alone to ME with LLND was not confirmed in the intent-to-treat analysis. ME with LLND had a lower local recurrence, especially in the lateral pelvis, compared to ME alone.
本研究旨在确认单纯直肠系膜切除术（ME）在疗效方面不劣于 ME 联合侧方淋巴结清扫术（LLND）。
临床 II 期或 III 期低位直肠癌偶尔会发生侧方骨盆淋巴结转移，日本标准手术方式为 ME 联合 LLND。然而，ME 联合 LLND 仅为国际标准的直肠癌手术方式。
纳入标准为组织学证实的临床 II/III 期直肠腺癌；主病灶位于直肠，下界低于腹膜反折；无侧方骨盆淋巴结肿大；体力状态评分 0 或 1 分；年龄 20 至 75 岁。患者术中随机分配行 ME 联合 LLND 或 ME 单独治疗。主要终点为无复发生存率，非劣效性边界为危险比 1.34。次要终点包括总生存和局部无复发生存。分析采用意向治疗。
共 701 例患者被随机分为 ME 联合 LLND 组（n = 351）和 ME 单独组（n = 350）。ME 联合 LLND 组和 ME 单独组的 5 年无复发生存率分别为 73.4%和 73.3%（危险比：1.07，90.9%置信区间 0.84-1.36），单侧 P 值<0.0547 提示非劣效性。ME 联合 LLND 组和 ME 单独组的 5 年总生存和局部无复发生存率分别为 92.6%和 90.2%，87.7%和 82.4%。ME 联合 LLND 组和 ME 单独组的局部复发患者分别为 26 例（7.4%）和 44 例（12.6%）（P = 0.024）。
在意向治疗分析中，未证实 ME 单独治疗不劣于 ME 联合 LLND。与 ME 单独治疗相比，ME 联合 LLND 侧方骨盆局部复发率更低，尤其是在侧方骨盆。
