Clinical Outcomes of Differentiated Thyroid Cancer With Gross Extrathyroidal Extension Into the Strap Muscles: A Case Control Study

Background: The 8th edition of the American Joint Committee on Cancer/tumor-node-metastasis (AJCC/TNM) staging system for differentiated thyroid cancer (DTC), implemented in January 2018, classifies patients >/= 55 years of age with gross extrathyroidal extension (ETE) of the primary tumor into the overlying strap muscles as prognostic stage II. However, it remains controversial as to whether or not gross ETE into the strap muscles is an independent predictor of recurrence, response to therapy, need for additional therapies, or overall survival. Using a case control study design, we evaluated the prognostic significance of gross ETE among adults. Methods: After obtaining IRB approval, we used the tumor registry at our institution to retrospectively identify 51 AJCC stage II patients with DTC aged >/= 55 years with gross ETE into only the strap muscles (51/2,225 patients). For each of the 51 cases, we identified one control who matched on all of the following important prognostic factors: age at diagnosis (± 5 years), sex, histology, size of tumor (± 1 cm), lymph node metastases, distant metastases, completeness of resection, receipt of radioactive iodine (RAI) therapy, and duration of follow-up (± 5 years). The controls (n=51) had no gross ETE. Results: In the 51 patients with gross ETE into only the strap muscles, the mean age at diagnosis was 64 years, 77% were female, 37% had lymph node metastases, and none had distant metastases. The average tumor size was 2.1 cm with the majority of patients (49/51) demonstrating papillary thyroid carcinoma (1 follicular thyroid carcinoma and 1 Hurthle cell thyroid carcinoma). Only 6% of patients (3/51) had incomplete resections and 92% (47/51) received RAI therapy. The mean duration of follow-up was 8 years. There were no statistically significant differences between the cases and controls on each of the pre-specified prognostic variables described in the methods. In addition, there were no statistically significant differences between the groups in terms of rates of recurrence: cases 18% (9/51) and controls 29% (15/51) (p=0.24), best response to initial therapy (excellent, biochemical incomplete, structural incomplete, or indeterminate response to therapy), and need for subsequent interventions including surgery, RAI, external beam radiation, or systemic therapy. Furthermore, there were no statistically significant differences between the cases and controls with respect to 10-year disease-free survival (cases 83% and controls 68%, p=0.90) and 10-year overall survival (cases 97% and controls 89%, p=0.10). Conclusions: In a case control analysis with a mean follow up of 8 years, the presence of ETE into the strap muscles was not an independent predictor of worse clinical outcomes in adults >/= 55 years old with DTC. These findings can be used to inform the future editions of the AJCC/TNM and American Thyroid Association staging systems for DTC.