Is Extrathyroidal Extension an Indicator of Poor Prognosis in Papillary Thyroid Cancer?

  • Clin Thyroidol 2022;34:75–77.
  • Background:
    • The incidence of papillary thyroid cancer (PTC) is increasing at a rapid rate:
      • Probably related to thyroid nodules being detected incidentally by more frequent radiologic studies being performed, and
      • Also likely due to a change in the molecular oncogenes:
        • Driving its development and progression
    • The standard initial treatments include:
      • Thyroidectomy and, in some instances, radioactive iodine therapy
    • The factors that assist in the decision for a particular treatment are multiple, but include:
      • Patient age
      • Gender
      • Histologic characteristics
      • Findings on radiologic and nuclear medicine studies
      • Postoperative serum thyroglobulin levels
    • One particular histologic finding:
      • Minor extra-thyroidal invasion:
        • Has been controversial regarding its relevance to recurrence and prognosis
      • Diker-Cohen et al performed a meta-analysis and noted that:
        • Minimal extrathyroidal extension:
          • Did increase the risk of recurrence, but not of mortality
      • Castagna et al also reported:
        • An increased risk of recurrence in patients with minimal extrathyroidal extension when compared to intrathyroidal tumors
      • In contrast, Ahmaddy et al and Raruenrom et al:
        • Did not find that minimal extrathyroidal extension was associated with a worse prognosis
    • In the current study, Forleo et al have investigated this issue, adding further understanding to the interpretation of minimal extrathyroidal invasion in patients with PTC
  • Methods:
    • The authors used the Italian Thyroid Cancer Observatory database to identify patients with PTC with minimal extrathyroidal extension and excluded patients who had local lymph node involvement with cancer
    • This database includes patient information prospectively collected from multiple medical centers
    • The authors identified 2,237 patients who fulfilled the study eligibility criteria and had at least 1 year of follow up
    • Multiple factors were evaluated, including the type of initial thyroid surgery, histologic variants of PTC, tumor diameter, risk stratification using the American Thyroid Association system, use and dose of radioactive iodine therapy and disease response
  • Results:
    • There were 1831 patients (81.8%) who had an excellent response, 296 (13.2%) an indeterminate response, 55 (2.5%) a biochemically incomplete response, and 55 (2.5%) a structurally incomplete response
    • Detailed evaluation indicate that, as individual factors:
      • Minimal extrathyroidal extension, tumor size larger than 2 cm, aggressive PTC histology, and age at diagnosis:
        • Were not found to be associated with a worse initial therapy response:
          • However, the combination of:
            • Minimal extrathyroidal extension and tumor size greater than 2 cm:
              • Was associated with a significantly worse outcome
      • Radioactive iodine therapy did not appear to improve prognosis
  • Conclusions:
    • Minimal extrathyroidal extension alone did not predict a worse prognosis in PTC patients who did not have cervical lymph node involvement in a large study cohort
    • However, it appears that the combination of tumor diameter larger than 2 cm and the presence of minimal extrathyroidal extension:
      • May help predict low-to-intermediate risk of recurrent or persistent disease
  • This study by Forleo et al helps further our understanding of the possible role of minimal extrathyroidal extension in PTC in predicting recurrent or persistent disease
  • The study has the attributes of analyzing a large group of patients, obtaining data from multiple medical centers at the time of initial surgery, of examining patients with no known cervical lymphadenopathy, and they used the ATA risk stratification system
  • However, there are also several aspects that should also be noted
  • There were multiple surgeons and pathologists, and there was not an independent pathologic review board that analyzed all of the samples
  • The study analyzed only the response at 1 year, but is apparently monitoring these patients over a longer duration
  • The definition of minimal extrathyroidal extension and its application in every case is not substantiated
  • In summary, I think it clinically relevant that this analysis of a large cohort of PTC patients found that minimal extrathyroidal extension alone is not a significant risk factor for recurrence, but when it is combined with tumor size > 2 cm, there appears to be a higher risk of recurrence
  • Radioactive iodine therapy did not seem to be beneficial, although there was a relatively low percentage of patients who received radioactive iodine and the statistical evaluation of this treatment was complex
  • I think it reasonable to consider all relevant laboratory, histology, radiologic and clinical factors on an individual basis to help decide whether radioactive iodine therapy may be warranted
  • In addition, performing a radioactive iodine scan with baseline and stimulated serum thyroglobulin levels may help in making this decision
  • References
    • Diker-Cohen T, Hirsch D, Shimon I, Bachar G, Akirov A, Duskin-Bitan H, Robenshtok E 2018 Impact of minimal extra-thyroid extension in differentiated thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab 103:2100–2106.
    • Castagna MG, Forleo R, Maino F, Fralassi N, Barbato F, Palmitesta P, Pilli T, Capezzone M, Brilli L, Ciuoli C, Cantara S, Formichi C, Pacini F 2018 Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor. J Endocrinol Invest 41:1029–1035.

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