hyroid cancer diagnoses are rising, with unresectable cases carrying poor prognosis. Neoadjuvant targeted therapy (TKI), along with minimally invasive radiofrequency ablation (RFA) or transarterial embolization (TAE), can reduce tumor burden, enabling surgery and preserving quality of life. This study evaluates their feasibility and outcomes in locally advanced unresectable thyroid cancers.

We retrospectively analyzed 17 patients (13 with differentiated thyroid cancer [DTC], 4 with anaplastic thyroid cancer [ATC]) treated at our medical center between November 2018 and July 2025. Inclusion criteria were untreated, inoperable thyroid cancer. Patients received neoadjuvant TKI alone or in combination with TAE and/or RFA. The primary endpoint was surgical conversion. Secondary outcomes included RECIST 1.1 response and change in surgical morbidity as measured by two metrics (the MGH/MEEI-MSK-MD Anderson [MMM] surgical morbidity complexity score and the Invasive Thyroid Class).

Among the 13 DTC patients (median age 71), 5 received neoadjuvant TKI combined with TAE and/or RFA, 6 received TKI alone, and 2 received only TAE plus RFA (no TKI). Surgical resection was achieved in 3 of 5 patients (60%) in the TKI + TAE/RFA group (2 R0 resection, 1 R1 resection), 2 of 2 patients (100%) in TAE plus RFA group (1 R0 resection, 1 R2 resection), and 1 of 6 TKI (17%) alone group (R2 resection). Overall response in the DTC cohort included 2 CR, 4 PR, and 4 SD. In the ATC cohort (all TKI), one patient achieved R0 resection after BRAF-targeted therapy. The mortality rate was 23%(3/13) in DTC and 50%(2/2) in ATC. The mean MMM scores were declined after neoadjuvant treatment compared with baseline.

This study emphasizes the promising role of combining targeted therapy with minimally invasive approaches like TAE and RFA as a neoadjuvant strategy for advanced thyroid cancers that are initially considered unresectable. However, treatment decisions should be tailored to each patient, carefully weighing therapeutic benefits against potential adverse effects, and ensuring active patient participation in the decision-making process.