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Elliot A Asare, Nancy D Perrier, Letter to the Editor: “An Analysis of the American Joint Committee on Cancer 8th Edition T Staging System for Papillary Thyroid Carcinoma”, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 9, September 2020, Pages e3488–e3489, https://doi.org/10.1210/clinem/dgz130
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We read with interest the manuscript by Tran et al (1), which assessed the prognostic performance of the American Joint Committee on Cancer (AJCC) 7th edition (2) versus the 8th edition (3) with regards to the tumor categories for papillary thyroid carcinoma (PTC). The authors found AJCC 7th edition to be superior to the AJCC 8th edition on all measures of model performance and attributed this difference to microscopic extrathyroidal extension (mETE).
There are important points worth noting with regards to staging and PTC. The removal of mETE from the 8th edition was based on several published studies that raised awareness about its limitations (4–8). Mete et al described the thyroid gland as lacking a homogenous, continuous full envelope to qualify as an encapsulated organ (4). Given the discontinuity of the pseudo-capsule around the thyroid gland, assigning mETE appears subjective. In a study by Su et al where 11 pathologists reviewed 69 scanned slides of PTC looking for mETE, there was wide inter- and intra-observer variability (5). If expert pathologists cannot make the consistent diagnosis of mETE, then continuing to include it in the tumor category definitions for PTC will be perpetuating the collection of arbitrary data.
Woolner et al first described the concept of gross extrathyroidal extension (ETE) in their series from the Mayo Clinic (1926–1955) and showed that tumor extension from the thyroid to the larynx, trachea, or esophagus carried a poor prognosis (7). The negative prognostic impact of gross ETE was further corroborated in a study of 1012 patients from Memorial Sloan Kettering Cancer Center from 1930 to 1985 (6). Andersen et al reported a 30-year disease specific survival rate of 29% for patients with gross ETE versus 87% for those without ETE. The local failure rate for patients with gross ETE was 47% versus 9% in the cohort without ETE (6). While gross extension of PTC into adjacent structures is prognostic, studies including the publication by Tran et al have not found mETE to be independently associated with worse survival outcome. Arora et al compared outcomes of 48 patients with mETE with that of 23 patients with macroscopic ETE (8). They reported an increased risk of recurrence and poor disease-free survival in the cohort with macroscopic ETE compared to mETE. There was no statistically significant difference in recurrence rate or disease-free survival between mETE and no ETE groups (8).
We do not agree with Tran et al on the call for the reintroduction of mETE into the staging system for well-differentiated thyroid carcinoma. Diagnosis of mETE is subjective, and it has not been found to be prognostic, likely due to the wide variation in diagnosis. We agree with the continued quest to improve the quality and prognostic impact of TNM staging for PTC using objectively defined criteria supported by high-quality data.
Additional Information
Disclosure Summary: No relevant financial disclosures. Nancy D. Perrier served as the chair of the endocrine disease site expert panel of the 8th edition of the American Joint Committee on Cancer. Elliot A. Asare was a member of the Editorial Board of the 8th edition of the American Joint Committee on Cancer and a member of the endocrine disease site expert panel of the 8th edition.
