Staging of Medullary Thyroid Carcinoma

  • Staging:
    • TNM staging:
      • The pathological tumor, node, metastasis (pTNM) criteria for clinical / pathologic tumor staging (eighth edition) adopted by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) are based upon:
        • Tumor size
        • The presence or absence of extra-thyroidal invasion
        • Local and regional nodal metastases
        • Distant metastases 
    • Stage I :
      • Medullary thyroid cancers (MTCs) that are equal or less than 2 cm in diameter without evidence of disease outside of the thyroid gland
    • Stage II:
      • Tumors  greater than 2 cm confined to the thyroid or tumors of any size without lymph node metastasis that demonstrate gross extrathyroidal extension invading only the strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles)
    • Stage III:
      • Tumors of any size demonstrating metastatic lymph node involvement in the central neck (levels VI or VII; pretracheal, paratracheal, or prelaryngeal/Delphian, or upper mediastinal lymph nodes) with or without gross invasion into the strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles)
    • Stage IV :
      • Any distant metastases, or lymph node involvement outside of the central neck (level VI/VII), or gross invasion into other structures of the neck (beyond just strap muscle involvement)
  • One study evaluated the prognostic significance of a previous TNM staging scheme in patients with MTC:
    • Most of whom were treated by total thyroidectomy and then followed for a median of four years:
      • Although the follow-up was short:
        • Mortality due to MTC was:
          • 0% stage I 
          • 13% in stage II
          • 56% in stage III
          • 100% in stage IV
  • A subsequent analysis of MTC patients using the National Cancer Database and the SEER (Surveillance, Epidemiology, and End Results) data set demonstrated that the seventh and eighth editions of the AJCC staging system:
    • Were associated with five-year overall survival rates of:
      • 95% in stage I
      • 91% in stage II
      • 89% in stage III
      • 68% in stage IV
    • Furthermore:
      • Disease-specific survival rates were:
        • 100% in stage I
        • 99%  in stage II
        • 97%  in stage III
        • 82% in stage IV
  • Dynamic risk stratification:
    • Using the same concepts that were initially developed for differentiated thyroid cancer:
      • Dynamic risk stratification for MTC allows clinicians to modify initial AJCC staging risk estimates over time based on:
         
        • The biological behavior the tumor and the response to therapy in individual patients
      • For application in MTC, the definitions of the response to therapy categories needed to be modified to utilize calcitonin and carcinoembryonic antigen (CEA) as tumor markers (rather than thyroglobulin):
        • At each follow-up visit, patients are classified as having one of the following clinical outcomes:
          • Excellent response:
            • An undetectable calcitonin and normal-range CEA in the absence of structurally identifiable disease
          • Biochemical incomplete response:
            • A detectable calcitonin or elevated CEA in the absence of structurally identifiable disease
          • Structural incomplete response:
            • The presence of recurrent or persistent structurally identifiable disease
    • In two retrospective studies examining MTC patients with a median of 5 to 7 years of follow-up:
      • An excellent response to therapy was associated with:
        • Structural disease recurrence rate of 1% to 4%
        • Biochemical recurrence rate of 11% to 15%
        • Disease-specific mortality of less than 3%
      • Patients with a biochemical incomplete response demonstrated a:
        • Structural disease recurrence rate of 32% to 37%
        • Biochemical recurrence rate of 51% to 53%
        • Disease-specific mortality of 11%
      • The poorest outcomes were seen in those patients with a structural incomplete response to initial therapy with:
        • Disease-specific mortality rates of 38% to 56%
  • The calcitonin and CEA doubling times:
    • Can also provide meaningful insights into:
      • Prognosis
      • Expected course of disease progression that can further refine these response to therapy assessments