Clinical Validation of the Prognostic Stage Groups of the Eighth-Edition TNM Staging for Medullary Thyroid Carcinoma

J Clin Endocrinol Metab. 2018 Dec 1;103(12):4609-4616. doi: 10.1210/jc.2018-01386.


Context: Despite advances in thyroid cancer staging systems, considerable controversy about the current staging system for medullary thyroid carcinoma (MTC) continues.

Objective: We aimed to evaluate the prognostic performance of the current eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control TNM staging system (TNM-8) and the alternative proposed prognostic stage groups based on recursive partitioning analysis (TNM-RPA).

Design, setting, and patients: We retrospectively analyzed 182 patients with MTC treated at a single tertiary Korean hospital between 1995 and 2015.

Interventions and main outcome measures: Survival analysis was conducted according to TNM-8 and TNM-RPA. The area under the receiver-operating characteristic curve (AUC), the proportion of variation explained (PVE), and the Harrell concordance index (C-index) were used to evaluate predictive performance.

Results: Under TNM-8, only two (1.1%) patients were downstaged compared with the seventh edition of the AJCC TNM staging system (TNM-7). The AUC at 10 years, PVE, and C-index were 0.679, 8.7%, and 0.744 for TNM-7 and 0.681, 8.9%, and 0.747 for TNM-8, respectively. Under TNM-RPA, 104 (57.14%) patients were downstaged compared with TNM-8. TNM-RPA had better prognostic performance with respect to cancer-specific survival (AUC at 10 years, 0.750; PVE, 20.9%; C-index, 0.881).

Conclusions: The predictive performance of the revised TNM-8 in patients with MTC has not changed despite its modification from TNM-7. The proposed changes in TNM-RPA were statistically valid and may present a more reproducible system that better estimates cancer-specific survival of individual patients.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Carcinoma, Neuroendocrine / mortality*
  • Carcinoma, Neuroendocrine / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Survival Analysis
  • Thyroid Gland / pathology*
  • Thyroid Neoplasms / mortality*
  • Thyroid Neoplasms / pathology

Supplementary concepts

  • Thyroid cancer, medullary