Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC)

SIMPLE SUMMARY: Microscopic extra-thyroidal extension (mETE) in papillary thyroid carcinoma (PTC) has shown no effect on survival but controversy remains regarding its impact on disease recurrence. As it was removed from the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) classification in 2017, PTC tumors previously classified as pT3 are now downstaged to pT1 and pT2 tumors. This might imply that such tumors now need less aggressive treatments, especially complementary radioactive iodine treatment. We ought to assess if mETE remains a poor prognosis risk factor that still needs to be taken into account in the post-operative treatment strategy. ABSTRACT: Background: This study assessed the risk of reduced disease-free survival (DFS) and poor clinical outcome in patients with papillary thyroid carcinomas (PTC) with microscopic extra-thyroidal extension (mETE), as compared to PTC patients without mETE. Methods: Retrospective analysis of a prospective database of patients treated by total thyroidectomy and radioactive iodine (RAI) with a five-year follow-up and tumors < 40 mm. In total, 303 patients were analyzed: 30.7% presented tumors with mETE, and 69.3% without. mETE was defined as extra-thyroidal invasion without skeletal muscle involvement. The primary outcome, DFS, was defined as the interval between initial treatment and any subsequent PTC-related treatment. The second outcome was the clinical status at five years. Results: In univariate analyses, the five-year DFS was significantly lower for tumors with mETE (62.4% versus 88.1%, p < 0.001). In multivariate analysis, mETE and massive lymph node involvement (LNI) were independent prognostic factors, associated respectively with a hazard ratio of 2.55 (95% CI 1.48–4.40) and 8.94 (95% CI 4.92–16.26). mETE was significantly associated with a pejorative clinical outcome at five years, i.e., biochemical/indeterminate response and structural persistence (Respectively OR 1.83 (95% CI 0.83; 4.06) and OR 4.92 (95% CI 1.87; 12.97)). Conclusion: Our results suggest that mETE is an independent poor prognosis factor of reduced DFS and predictive of poor clinical outcome.