Neoadjuvant tyrosine kinase inhibitor therapy for unresectable locally advanced thyroid cancer: A systematic review and meta-analysis.

e18151 Background: Unresectable locally advanced thyroid cancers represent a rare clinical entity with a poor prognosis compared with early-stage disease. The absence of complete surgical resection is associated with markedly reduced five-year survival. In this context, neoadjuvant tyrosine kinase inhibitors (TKIs) have emerged as a strategy to induce tumor downstaging and facilitate surgical resection. In tumors with actionable genomic alterations, this approach may convert unresectable disease to resectable or allow less extensive surgery with reduced morbidity. Methods: We systematically searched PubMed, Embase, and Cochrane for studies (cohorts and clinical trials) evaluating neoadjuvant TKI therapy in adults with locally advanced, unresectable thyroid cancer, regardless of histology subtype. Studies evaluating adjuvant or purely palliative TKI therapy, other systemic treatments, combination regimens involving TKIs, and overlapping patient populations were excluded. All analyses were performed using R software (version 4.5.2). Pooled proportions were estimated using random-effects models, with heterogeneity assessed via I² statistics and Cochran’s Q test. Results: Among 1,053 screened records, six studies (five phase II clinical trials and one retrospective cohort) met the inclusion criteria, encompassing 144 patients, of whom 51.1% were male. All patients had locally advanced differentiated thyroid cancer and were treated with anlotinib, lenvatinib, apatinib, or selpercatinib. The reported median follow-up ranged from 6 to 34 months. The pooled R0/R1 resection rate was 81.8% (95% CI, 61.9–92.6; I² = 57.1%). The pooled objective response rate was 47% (95% CI, 38.7–55.5; I² = 26.1%). Partial responses were observed in 50.5% of patients (95% CI, 39.8–61.1; I² = 22.7%), while stable disease occurred in 46.4% (95% CI, 28.8–64.9; I² = 50.5%), resulting in a disease control rate of 95% (95% CI, 86.7–98.2; I² = 0%). Any-grade adverse events were reported in 89% of patients (95% CI, 60.9–97.7; I² = 50.1%) across three studies, with hypertension being the most frequently observed toxicity. Conclusions: In this rare disease setting, neoadjuvant TKI therapy demonstrated meaningful antitumor activity and enabled surgical resection in a substantial proportion of patients with initially unresectable thyroid cancer. However, evidence is limited by small cohorts, short follow-up, and high adverse event rates, highlighting the need for prospective studies to optimize patient selection.