**E**ff**ects of the Minimal Extrathyroidal Extension on Early Response Rates after (Adjuvant) Initial Radioactive Iodine Therapy in PTC Patients**

**Freba Ahmaddy 1,**†**, Vera Wenter 1,**†**, Harun Ilhan 1, Daniel Wacker 1, Marcus Unterrainer 1, Thomas Knösel 2, Peter Bartenstein 1, Christine Spitzweg 3, Sebastian Lehner 1,4 and Andrei Todica 1,\***


Received: 11 September 2020; Accepted: 11 November 2020; Published: 13 November 2020

**Simple Summary:** The aim of our retrospective study was to evaluate the impact of minimal extrathyroidal extension on early response rate after (adjuvant) initial radioactive iodine therapy in patients with papillary thyroid cancer (PTC). We found that response rates after radioactive iodine (RAI) therapy in PTC patients were achieved irrespective of minimal extrathyroidal extension (mETE). Nonetheless, the risk of lymph node metastases involvement was significantly higher in the mETE patient group.

**Abstract:** Background: Extrathyroidal extension of differentiated thyroid cancer is a poor outcome factor but seems to be less significant in minimal extrathyroidal extension (mETE). However, the impact of mETE on response rate after (adjuvant) initial radioactive iodine (RAI) therapy remains unclear. We therefore compared response rates of patients with classical and follicular variants of papillary thyroid cancer (PTC) according to the updated eighth tumor-node-metastasis (TNM) classification to a control group. Methods: 455 patients with T3 (primary tumor > 4 cm) PTC according to the seventh classification who underwent total thyroidectomy followed by RAI therapy were screened. Patients formerly classified as T3 PTC solely due to mETE were reclassified into patients with T1 (primary tumor ≤ 2 cm) or T2 (primary tumor > 2 cm but ≤ 4 cm) +mETE and compared to a control group of T1/T2 −mETE PTC patients. Results: 138/455 patients were reclassified as T1/2 +mETE and compared to 317/455 T1/T2 −mETE control patients. At initial presentation, +mETE patients showed significantly higher rates of cervical lymph node metastases (*p*-value 0.001). Response rates were comparable in both groups (*p*-value n.s.). N1a/N1b-stage (Hazard ratio, HR 0.716; 95% CI 0.536–0.956, *p*-value 0.024) was identified as an independent prognostic factor for lower response rates. Conclusion: Response rates after RAI therapy were comparable in PTC patients irrespective of mETE but with higher rates of lymph node metastases.

**Keywords:** differentiated thyroid cancer; papillary thyroid cancer; minimal extrathyroidal extension; radioactive iodine therapy
