Neoadjuvant Therapy with Multikinase Inhibitors for Locally Advanced Differentiated Thyroid Cancer: A Systematic Review

Background: The use of multikinase inhibitors (MKIs) in thyroid cancer has been established to downsize and facilitate resection of poorly differentiated, differentiated high-grade, anaplastic, and medullary thyroid cancer. Case reports and case series have suggested the potential use of MKIs as neoadjuvant therapies for locally advanced differentiated thyroid cancer (DTC). Our objective was to review available studies and assess if neoadjuvant therapy with MKI can improve surgical and oncological outcomes in patients with locally advanced DTC. Methods: A systematic search of four different databases (PubMed, Cochrane Library, Scopus, and EMBASE) with no time restrictions was performed to identify relevant observational studies evaluating patients with locally advanced DTC who received neoadjuvant therapy before surgery with MKI (PROSPERO ID: CRD420251012812). Results: A total of 119 participants from 23 observational studies (12 case reports, 9 case series, and 2 prospective phase II studies) were included. Lenvatinib was the most frequently used MKI, followed by sorafenib. Tumor volume reduction ranged from 25% to 87%, and partial response rates ranged between 33.3% and 76.9%, whereas progressive disease was described only in seven cases. Of 114 patients with inoperable or potentially resectable tumors with associated high perioperative morbidity, 95 (83.3%) were able to undergo surgery. Conclusions: Neoadjuvant MKIs in locally advanced DTC may improve resection rates. The overall low quality of evidence prompts further prospective studies to confirm these findings.