RESUMEN
Background: Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer with limited treatment options for advanced disease. A small subset exhibits mixed MTC histology with both medullary and well-differentiated components. We investigated survival outcomes with systemic therapy in isolated versus mixed MTC using a large population-based cohort. Methods: Patients diagnosed with MTC from 2000 to 2019 were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. The overall and thyroid cancer-specific survivals were compared between isolated (n = 1814) and mixed (n = 113) MTC cohorts. The impact of postoperative systemic therapy on survival was analyzed. Results: No significant difference in 10-year overall survival was observed between isolated (77.4 %) and mixed (75.2 %) MTC in a cohort of 1927 patients. Median overall survival was similar between isolated (136.9 months) and mixed MTC (129.0 months), p = 0.81. While systemic therapy improved 10-year survival in isolated MTC (83.2 % vs. 76.9 %, p < 0.001), no benefit was seen in mixed MTC (76.4 % vs. 74.2 %, p = 0.82). Multivariate analysis confirmed survival gains with systemic therapy for isolated (HR = 0.763, 95%CI = 0.590-0.987, p = 0.040) but not mixed MTC (HR = 0.909, 95%CI = 0.268-3.079, p = 0.88). Conclusions: In this large population-based study, no significant survival difference was observed between isolated and mixed MTC. Systemic therapy was associated with improved survival in isolated MTC, but not in the mixed subtype. These findings suggest a differential treatment response that warrants further investigation in prospective studies and may inform histology-tailored management strategies for mixed MTC.