Anaplastic thyroid carcinoma (ATC) remains rare (<2% of thyroid cancers) but disproportionately lethal, accounting for >50% of thyroid cancer mortality. Contemporary strategies driven by genomics and multimodal therapy are reshaping outcomes
Multimodal Neoadjuvant Strategies
Contemporary management prioritizes urgent molecular profiling, particularly for BRAF V600E mutations, identified in approximately 20–50% of ATC cases.
BRAF-positive ATC receives dabrafenib plus trametinib, enabling tumor downsizing for resection in previously inoperable cases. BRAF-negative tumors benefit from multikinase inhibitors like lenvatinib combined with immunotherapy (pembrolizumab), achieving partial responses in 40-60% and median overall survival extending to 9 months.
Surgical and Systemic Integration
Surgery remains a cornerstone of management following favorable neoadjuvant response, with R0 resection margins strongly associated with improved survival outcomes. In advanced and metastatic disease, targeted therapies and immunotherapy have largely replaced conventional cytotoxic chemotherapy.
Adjuvant or definitive radiotherapy plays a critical role in locoregional control, particularly for airway compromise, esophageal invasion, and symptomatic palliation.
Emerging Prognostication and Outcomes
Prognostic refinement now incorporates tumor microenvironment profiling, including PD-L1 expression, which may predict response to immunotherapy. Additionally, socioeconomic and healthcare access factors significantly influence outcomes, particularly in resource-variable settings such as India.
With the adoption of molecularly driven multimodal strategies, median survival has improved from historical figures of 3–4 months to approximately 8–12 months in selected patients.