title: Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial.
abstract: 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.
authors.affiliation: *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.
authors.forename: Shin
authors.initials: S
authors.lastname: Fujita
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Kanemitsu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kinugasa
authors.forename: Koji
authors.initials: K
authors.lastname: Komori
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohue
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Ota
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Akazai
authors.forename: Manabu
authors.initials: M
authors.lastname: Shiozawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Bandou
authors.forename: Kenji
authors.initials: K
authors.lastname: Katsumata
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Akagi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takiguchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Saida
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Akasu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Moriya
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008197:Lymph Node Excision / Q000009:adverse effects; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011183:Postoperative Complications; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D012007:Rectum / Q000601:surgery*; D016896:Treatment Outcome; D055815:Young Adult