Real-World outcomes and prognostic factors in anaplastic thyroid cancer: Evidence from the REGETNE-Thyroid cohort

BACKGROUND: Anaplastic thyroid cancer (ATC) is an extremely rare cancer with very poor prognosis. Targeted therapies have improved outcomes in selected patients, but molecular testing is often difficult because of the aggressive course, rapid clinical deterioration, and long turnaround times. This study aimed to provide real-world evidence on the management and outcomes of ATC and to evaluate the prognostic impact of molecular testing. MATERIALS AND METHODS: This multicentric, retrospective study included patients diagnosed with ATC between 1992-2024 from the REGETNE-Thyroid Network. Factors associated with overall survival (OS) were analyzed using Cox proportional hazards models. RESULTS: 214 patients were included (median age 70.8 years; 56.5% female). Median OS was 4.5 months. Access to molecular testing (HR 0.42, p = 0.001) and BRAF V600E mutation (HR 0.50, p = 0.008) were associated with longer OS, whereas TERT promoter mutations were associated with shorter survival (HR 2.80, p = 0.014). Local surgery showed a favorable prognostic association, regardless of stage (IVa/IVb: HR 0.54, p = 0.026; IVc: HR 0.36, p 95%) in BRAF V600E-mutated ATC, was also associated with longer survival (HR 0.40; p = 0.001). CONCLUSION: Molecular testing was associated with improved survival in ATC, likely driven by the identification of actionable alterations with effective targeted therapies. Local management is key in all stages. Our findings also support immunotherapy, tyrosine kinase inhibitors and their combinations as key therapeutic options.