title: A proposal for combination of total number and anatomical location of involved lymph nodes for nodal classification in non-small cell lung cancer.
abstract: BACKGROUND
  We previously reported the prognostic impact of the number of involved lymph nodes (LNs) on survival in non-small cell lung cancer (NSCLC). However, it remains unknown whether the total number or anatomic location of involved LNs is a superior prognostic factor.
  
  
  METHODS
  A total of 689 patients with NSCLC who underwent complete resection involving dissection of the hilar and mediastinal LNs with curative intent of ≥ 10 LNs were enrolled. The association between the total number of LNs (nN) involved and survival was assessed by comparison with the anatomic location of LN involvement (pathologic lymph node [pN]), the present nodal category.
  
  
  RESULTS
  We classified the patients into five categories according to the combined pN and nN status as follows: pN0-nN0, pN1-nN1-3, pN1-nN4-, pN2-nN1-3, and pN2-nN4. Although there was no statistically significant difference between the pN1-nN4- and pN2-nN1-3 categories, pN2-nN1-3 had better prognoses than pN1-nN4-. On multivariate analysis, the nN category was an independent prognostic factor for overall survival and disease-free survival (vs nN4-; the hazard ratios of nN0 and nN1-3 for overall survival were 0.223 and 0.369, respectively, P &lt; .0001 for all), similar to the pN category. We propose a new classification based on a combination of the pN and nN categories: namely, N0 becomes pN0-nN0, the N1 category becomes pN1-nN1-3, the N2a category becomes pN2-nN1-3 + pN1-nN4-, and the N2b category becomes pN2-nN4. Each survival curve was proportional and was well distributed among the curves.
  
  
  CONCLUSIONS
  A combined anatomically based pN stage classification and numerically based nN stage classification is a more accurate prognostic determinant in patients with NSCLC, especially in the prognostically heterogeneous pN1 and pN2 cases. Further large-scale international cohort validation analyses are warranted.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan. Electronic address: saji-q@ya2.so-net.ne.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Saji
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuboi
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Matsubayashi
authors.affiliation: Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nagao
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kakihana
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Usuda
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kajiwara
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ohira
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000601:surgery; D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate