Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia

The aim of our retrospective study was to evaluate the outcome of patients with metastatic medullary thyroid cancer (MTC) treated with tyrosine kinase inhibitors (TKIs) and/or chemotherapy with the emphasis on analysis on the cohort treated by induction TKI because of locally advanced metastatic MTC. We analyzed the outcome of 30 patients (21 males, 9 females; median age 63.8 years) with metastatic MTC treated between 2000–2020. Sunitinib was used in 20 patients. Median progression-free survival on TKI and on chemotherapy was 10.6 (95% CI 7.1–14) months and 3.5 (95% CI 1.4–5.5) months, respectively. Median overall survival from diagnosis and from metastasis presentation was 38.2 (95% CI 4.7–71.7) months and 20.9 (95% CI 13.8–27.9) months, respectively. Eight patients (five females, three males; 58–86 years of age, median age 70 years) were treated with induction TKI because of inoperable locally advanced and metastatic MTC. The response rate to induction TKI was 50%; two patients (25%) had stable disease, and two patients (25%) had progressive disease. Our data support a new paradigm that TKIs may be the first treatment option in selected patients with locally advanced metastatic MTC, followed by locoregional treatment with surgery and/or external beam radiotherapy. Further studies are required to consolidate the presented data. A new paradigm of surgery after neoadjuvant/induction tyrosine kinase inhibitors is not accepted as a standard of care in patients with medullary thyroid cancer. The aim of our retrospective study was to evaluate the outcome of all patients with metastatic medullary cancer treated in a 20-year period in Slovenia and, among these, the cohort treated with induction tyrosine kinase inhibitors because of locally advanced metastatic medullary thyroid cancer. Our first hypothesis was that the outcome of metastatic medullary cancer treated with tyrosine kinase inhibitors is better than in those treated with chemotherapy. Our second hypothesis was that induction therapy with tyrosine kinase inhibitors was effective in the treatment of initially inoperable primary tumors. In the treatment of metastatic medullary cancer a systemic therapy was used in 83.4% (25/30) patients. Patients on targeted treatment with tyrosine kinase inhibitors had more often a partial remission than on chemotherapy (65% vs. 17%, respectively). Eight patients were treated with induction tyrosine kinase inhibitors because of locally advanced metastatic disease. The computer tomography evaluation of the primary tumor during tyrosine kinase inhibitor therapy revealed partial response in four cases and stable disease in four cases, but surgery was performed in two cases only. Our data support a new paradigm that tyrosine kinase inhibitors may be the first treatment option in patients with locally advanced metastatic medullary thyroid carcinoma followed by locoregional treatment with surgery and/or external beam radiotherapy. However, further studies are required to consolidate the presented data.