title: Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification.
abstract: BACKGROUND
  Adrenocortical carcinoma (ACC) is a rare malignancy, and it was only in 2004 that the International Union Against Cancer (UICC) defined TNM criteria and published the first staging classification. However, to date, the prognostic value of the proposed classification has not been evaluated.
  
  
  METHODS
  The German ACC Registry comprising 492 patients was searched for patients who were diagnosed between 1986 and 2007 with detailed information on primary diagnosis and a minimum follow-up of 6 months. Patients were assigned to UICC tumor stage, and disease-specific survival (DSS) was assessed. In addition, the contribution of potential risk factors for DSS was evaluated.
  
  
  RESULTS
  In total, 416 patients with a mean follow-up of 36 months met the inclusion criteria (stage I, n=23 patients; stage II, n=176 patients; stage III, n=67 patients; stage IV, n=150 patients). Kaplan-Meier analysis revealed a stage-dependent DSS. However, DSS in patients with stage II ACC did not differ significantly from DSS in patients with stage III ACC (hazard ratio, 1.38; 95% confidence interval, 0.89-2.16). Furthermore, patients who had stage IV ACC without distant metastases had an improved DSS compared with patients who had metastatic disease (P=.004). An analysis of different potential risk factors for defining stage III ACC revealed important roles in DSS for tumor infiltration in surrounding tissue, venous tumor thrombus (VTT), and positive lymph nodes; whereas tumor invasion in adjacent organs carried a prognosis similar to that of infiltration in surrounding tissue only.
  
  
  CONCLUSIONS
  The 2004 UICC staging classification for ACC has significant limitations. On the basis of the current analysis, a revised classification with superior prognostic accuracy is proposed (the European Network for the Study of Adrenal Tumors classification). In this system, stage III ACC is defined by the presence of positive lymph nodes, infiltration of surrounding tissue, or VTT; and stage IV ACC is restricted to patients with distant metastasis.
authors.affiliation: Department of Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Würzburg, Würzburg Germany. fassnacht_m@medizin.uni-wuerzburg.de
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Sarah
authors.initials: S
authors.lastname: Johanssen
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Peter
authors.initials: P
authors.lastname: Bucsky
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Mueller
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
mesh_terms: D018268:Adrenocortical Carcinoma / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000145:classification*; D011379:Prognosis; D012307:Risk Factors