title: A prospective multi-institutional validity study to evaluate the accuracy of clinical diagnosis of pathological stage III gastric cancer (JCOG1302A).
abstract: BACKGROUND
  Neoadjuvant chemotherapy (NAC) followed by radical surgery is a promising strategy to improve survival of patients with stage III gastric cancer, but is associated with the risk of preoperative overdiagnosis by which patients with early disease may receive unnecessary intensive chemotherapy.
  
  
  METHODS
  We assessed the validity of a preoperative diagnostic criterion in a prospective multicenter study. Patients with gastric cancer with a clinical diagnosis of T2/T3/T4, M0, except for diffuse large tumors and extensive bulky nodal disease, were eligible. Prospectively recorded clinical diagnoses (cT category, cN category) were compared with postoperative pathological diagnoses (pT category, pN category, and pathological stage). The primary endpoint was the proportion of pathological stage I tumors among those diagnosed as cT3/T4, which we expected to be 5% or less.
  
  
  RESULTS
  Data from 1260 patients enrolled from 53 institutions were analyzed. The proportion of pathological stage I tumors in those with a diagnosis of cT3/T4 (primary endpoint) was 12.3%, which was much higher than the prespecified value. The positive predictive value and the sensitivity for pathological stage III tumors were 43.6% and 87.8% respectively. The sensitivity and specificity of contrast-enhanced CT for lymph node metastasis were 62.5% and 65.7% respectively. After exploring several diagnostic criteria, we propose, for future NAC trials in Japan, a diagnosis of "cT3/T4 with cN1/N2/N3," by which inclusion of pathological stage I tumors was reduced to 6.5%, although its sensitivity for pathological stage III tumors decreased to 64.5%.
  
  
  CONCLUSIONS
  Clinical diagnosis of T3/T4 tumors was not an optimal criterion to select patients for intensive NAC trials because more than 10% of patients with pathological stage I disease were included. We propose the criterion "cT3/T4 and cN1/N2/N3" instead.
authors.affiliation: Gastric Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tfukagaw@ncc.go.jp.
authors.forename: Takeo
authors.identifier: http://orcid.org/0000-0002-9425-3767
authors.initials: T
authors.lastname: Fukagawa
authors.affiliation: Gastric Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katai
authors.affiliation: JCOG Data Center/Operations Office, National Cancer Center, Tokyo, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.affiliation: JCOG Data Center/Operations Office, National Cancer Center, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Digestive Surgery, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sano
authors.affiliation: Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Fukushima
authors.affiliation: Department of Surgery, Nagaoka Chuo General Hospital, Nagaoka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kawachi
authors.affiliation: Gastric Surgery Division, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Surgery, Sakai City Medical Center, Sakai, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yabusaki
authors.affiliation: Department of Surgery, Keiyukai Sapporo Hospital, Sapporo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan.
authors.forename: Sang-Woong
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Gastroenterological Surgery, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Division of Upper Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sasako
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging / Q000379:methods*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*
keywords: Clinical diagnosis; Clinical trial; Gastric cancer; Neoadjuvant chemotherapy