title: Optimal cut-off age in the TNM Staging system of differentiated thyroid cancer: is 55 years better than 45 years?
abstract: OBJECTIVE
  Age >45 years is included as a variable in the tumor, node, metastases (TNM) staging of differentiated thyroid cancer (DTC), but a higher cut-off value has been suggested to be more clinically relevant and prevent over-staging. We evaluated the optimal age cut-off to predict disease-specific survival (DSS) in patients with DTC.
  
  
  METHODS
  This cohort study included 6333 patients with DTC who underwent thyroid surgery at two tertiary referral centres between 1996 and 2005. The optimal age cut-off value between 45 and 65 years for prediction of DSS was assessed. The proportion of variation explained (PVE) and Harrell's c-index was calculated to compare the predictability of each model.
  
  
  RESULTS
  The median age of patients was 46·0 years (IQR 37·8-54·6), and 5498 (87%) were female. Median follow-up period was 10·0 years, and 10-year DSS rate was 98%. Using TNM staging with 45 years as the cut-off (TNM45), 10-year DSS rates of stage I-IV were 99·4%, 96·1%, 97·7% and 85·9%, respectively (PVE = 3·0%, Harrell's c-index = 0·693); and using 55 years as the cut-off (TNM55), 99·4%, 92·2%, 95·3% and 79·7%, respectively (PVE = 4·3%, Harrell's c-index = 0·776). On receiver operating characteristic curve analysis, the optimal age cut-off for prediction of DSS was 55·4 years (area under the curve = 0·837, P < 0·001). About 20% of patients were down-staged to stage I using TNM55 compared to that using TNM45.
  
  
  CONCLUSIONS
  The cut-off age of 55 years was more appropriate for TNM staging to achieve better predictability for DSS in patients with DTC. This change would prevent over-staging in low-risk patients and prevent over-aggressive treatment.
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Mijin
authors.initials: M
authors.lastname: Kim
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Suyeon
authors.initials: S
authors.lastname: Park
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyemi
authors.initials: H
authors.lastname: Kwon
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Jeon
authors.affiliation: Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Korea.
authors.forename: Hyeon Seon
authors.initials: HS
authors.lastname: Ahn
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
authors.forename: Sin-Ho
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shong
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Tae Hyuk
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods* / Q000401:mortality / Q000592:standards; D011379:Prognosis; D012372:ROC Curve; D018570:Risk Assessment; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*