title: A proposal for a TNM staging system for extramammary Paget disease: Retrospective analysis of 301 patients with invasive primary tumors.
abstract: BACKGROUND
  Although extramammary Paget disease (EMPD) usually appears as carcinoma in situ, it sometimes becomes invasive (iEMPD) and fatal. However, a TNM staging system for iEMPD has yet to be established.
  
  
  OBJECTIVE
  The aim of this study was to establish a TNM staging system for iEMPD.
  
  
  METHODS
  We retrospectively collected iEMPD patients treated at 12 institutes in Japan. Factors reported to be associated with survival such as distant metastasis, lymph node (LN) metastasis, and primary tumor status were evaluated using the log-rank test.
  
  
  RESULTS
  We enrolled 301 iEMPD patients, of whom 114 had remote metastases (49 had both distant and LN metastasis; 2, distant metastasis only; and 63, LN metastasis only) and the remaining 187 patients had no remote metastasis. Distant metastasis (M1) showed worse survival (P<0.00001). In the analysis of the 250 patients without distant metastasis, LN metastasis also showed worse survival (P<0.00001). Among the patients with LN metastasis, 2 or more LN metastases (N2) showed worse survival than did single LN metastasis (N1, P=0.02). Lastly, in the analysis of the 187 patients without metastasis, tumor thickness of over 4mm or lymphovascular invasion showed worse survival (T2, P<0.05 and P<0.001, respectively). Patients with neither of these features were defined as T1. From these results, we propose this TNM staging system: stage I, T1N0M0; stage II, T2N0M0; stage IIIa, anyTN1M0; stage IIIb, anyTN2M0; stage IV, anyTanyNM1. Other than stages II and IIIa, each stage had a statistically distinct survival curve.
  
  
  CONCLUSIONS
  We propose a TNM staging system for EMPD using simple factors for classification that could provide important prognostic information in managing EMPD. However, accumulation of more patient data and further revision of the system are required.
authors.affiliation: Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Japan; Toranomon Hospital, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ohara
authors.affiliation: University of Tsukuba, Japan. Electronic address: fujisan@md.tsukuba.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Shizuoka Cancer Center, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kiyohara
authors.affiliation: University of Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.affiliation: Hyogo Cancer Center, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Murata
authors.affiliation: University of Shinshu, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Uhara
authors.affiliation: Toyama Prefectural Central Hospital, Japan.
authors.forename: Naohito
authors.initials: N
authors.lastname: Hatta
authors.affiliation: University of Kyushu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.affiliation: University of Kagoshima, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Niigata Cancer Center Hospital, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: University of Hokkaido, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: University of Kanazawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: University of Tsukuba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging / Q000379:methods*; D010145:Paget Disease, Extramammary / Q000145:classification / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
keywords: Distant metastasis; Extramammary paget disease; Invasive; Lymph node metastasis; Lymphovascular invasion; Prognosis; TNM staging system; Tumor thickness