Application of neoadjuvant treatment in locally advanced thyroid cancer

CHEN Jia-ying; WANG Yu

doi:10.19538/j.cjps.issn1005-2208.2025.09.08

Abstract：Locally advanced thyroid carcinoma(LATC)accounts for 5％-15％of thyroid cancers and often involves adjacent critical nerves,vessels,and organs,resulting in surgical challenges and poor prognosis.Histologic subtypes include papillary thyroid carcinoma,follicular carcinoma,oncocytic carcinoma,poorly differentiated thyroid carcinoma(PDTC),anaplastic thyroid carcinoma(ATC),and high-grade medullary thyroid carcinoma(MTC).At the molecular level,activation of driver genes such as BRAF,RAS,and RET,together with mutations in TP53 and the TERT promoter,is closely associated with the aggressive behavior of LATC.Neoadjuvant therapy has emerged as a novel strategy,aiming to downstage tumors preoperatively,increase resectability,improve functional preservation,and prolong survival.Multitarget tyrosine kinase inhibitors(mTKIs),such as anlotinib and lenvatinib,and highly selective targeted agents,such as RET inhibitors(selpercatinib and pralsetinib),have demonstrated high objective response rates(ORR)in LATC neoadjuvant therapy,with some cases achieving R0 resection.For ATC with BRAF V600E mutation,preoperative therapy with dabrafenib plus trametinib has significantly improved survival.In the field of immunotherapy,programmed death-1(PD-1)and programmed death-ligand 1(PD-L1)inhibitors,either as monotherapy or in combination with targeted therapy,have shown potential efficacy in ATC and PDTC.Although evidence of efficacy is accumulating,optimal timing and management of adverse effects remain to be clarified.Future multicenter clinical studies are needed to establish individualized neoadjuvant therapy systems based on molecular subtyping,thereby advancing LATC toward precision and standardized treatment.