ABSTRACT Objectives Surgery is the definitive treatment for most thyroid cancers. However, anaplastic thyroid carcinoma (ATC) and other undifferentiated thyroid cancers are often unresectable and carry high mortality. Case reports and series have described neoadjuvant therapies, including chemotherapy, targeted therapy, radiation, and radioactive iodine, to improve resectability. This review evaluates the efficacy and safety of neoadjuvant therapy in unresectable thyroid cancers. Data Sources PubMed, Embase, and Web of Science. Review Methods A comprehensive literature search was performed through August 2025 following PRISMA‐ScR guidelines. English‐language studies reporting patient‐specific data on thyroid cancer diagnosis and neoadjuvant treatment were included. Using Covidence, patient demographics, neoadjuvant therapies, surgical interventions, and outcomes were extracted from 87 studies following inclusion and exclusion criteria. Results Individual patient data were available for 122 patients from 61 studies. The most common cancers were papillary thyroid carcinoma (PTC), ATC, and differentiated thyroid carcinoma (DTC). The median age was 61 years, 54% female. TNM staging was 68% T4, 69% N1, and 51% M0. Frequent mutations included BRAFV600E ( N = 31), RET ( N = 18), TERT ( N = 12), and TP53 ( N = 12). Lenvatinib ( N = 46) and dabrafenib and trametinib ( N = 26) were the most used. Total thyroidectomy occurred in 53% of patients. Post‐neoadjuvant therapy outcomes included partial response (64%) and complete response (10%), with subsequent R0 ( N = 62), R1 ( N = 38), and R2 ( N = 10) surgical resections. Conclusion Neoadjuvant therapy shows promise in improving resectability for unresectable and poorly differentiated thyroid cancers, with 51% of patients achieving R0 resection. Future studies should investigate optimal therapy selection, timing, dosing, and long‐term outcomes, including disease‐specific survival and patient‐reported measures. Level of Evidence NA.
Herzog et al. (Tue,) studied this question.