Familial Differentiated Thyroid Carcinoma Shows Comparable Radioiodine Treatment Outcomes to Sporadic Disease under Standard Protocols

Abstract Background Existing studies suggest that familial differentiated thyroid carcinoma (FDTC) may exhibit greater aggressiveness and poorer prognosis compared to sporadic differentiated thyroid carcinoma (SDTC). However, there remains no clear consensus regarding specific clinicopathological manifestations of invasiveness and the necessity for additional therapeutic interventions in FDTC. Thus, we implemented a retrospective cohort study to compare FDTC and SDTC through comprehensive clinicopathological profiling and RAIT outcome. Methods This retrospective cohort study compared 138 FDTC patients with 4816 SDTC controls through comprehensive clinicopathological profiling. Propensity score matching (PSM) was employed to assess the outcomes of radioiodine therapy (RAIT). Results FDTC exhibited a higher incidence of tumor bilaterality (46.4% vs 38.0%, P  = 0.047) and the BRAF V600E mutation rates (85.5% vs 78.0%, P  = 0.046), but lower frequencies of capsular, vascular, and lateral lymph node invasion. In FDTC, having > 5 metastatic lymph nodes was an independent risk factor for RAIT outcomes (HR: 2.68, 95%CI: 1.10–6.52, P  = 0.03). While the family history was not correlated with RAIT efficacy ( P  = 0.154), and overall disease-free survival (DFS) was comparable between FDTC and SDTC ( P  = 0.140). Furthermore, FDTC families with ≥ 3 affected members exhibited larger metastatic lymph node diameters (1.1cm vs 0.6 cm, P  = 0.014), higher lymph node burden (median 9 vs 4 nodes, P  = 0.013) and shorter DFS ( P  = 0.004). Conclusion FDTC presented unique biological behaviors, including increased bilaterality and the BRAF V600E mutation, yet achieved comparable RAIT outcomes to SDTC under standard protocols. However, FDTC with ≥ 3 affected members showed higher aggressiveness and poor prognosis, which may warrant intensified management.