OBJECTIVE: Compared with those of sporadic differentiated thyroid cancer (SDTC), the tumor characteristics of familial nonmedullary thyroid cancer (FNMTC) remain debatable. In addition, there is a paucity of data suggesting that their response to radioactive iodine (RAI) therapy differs from that of SDTC. We aimed to determine whether FNMTC is a homogenous biological entity that differs from SDTC in RAI therapy. METHODS: We retrospectively analyzed patients who underwent adjuvant ablative iodine radiotherapy between July 2016 and March 2020. We compared the differences in clinicopathological features and prognoses between the FNMTC and SDTC groups. The endpoint of the study was the rate of therapeutic response after 1 and 3 years of follow-up after first-line treatment. The response to therapy was classified into four categories: excellent response (ER), biochemical incomplete response (BIR), structural incomplete response (SIR) and indeterminate response (IDR). In addition, we conducted a meta-analysis of cohort studies to investigate the clinical outcomes. RESULTS: Of all the patients (n = 1758), 109 (6.2%) were classified as having FNMTC, whereas the remaining 1649 (93.8%) had SDTC. A greater proportion of FNMTC patients presented with extrathyroidal extension, capsular invasion, and multifocality (P = 0.01). In addition, patients with FNMTC were more likely to have advanced primary tumor stage and lymph node metastasis, but the differences were not statistically significant. At the end of follow-up (median follow-up of 3 years), the response to RAI therapy was significantly different between the two groups (ER: 66.1% vs 74.3%
IDR: 9.2% vs 12.1%
SIR: 14.7% vs 7.1%
BIR: 10.1% vs 6.5%). Moreover, patients with FNMTC more frequently presented evidence of disease than patients with SDTC did. However, the disease-free survival of patients with FNMTC was not shorter than that of patients with SDTC (P ≥ 0.05). CONCLUSION: Patients with FNMTC more often have aggressive characteristics at presentation and relatively worse clinical outcomes after RAI therapy. However, there was no statistically significant difference in the recurrence rate in the short-term follow-up. Considering that, FNMTC patients may be required more aggressive treatment approaches and closer postoperative monitoring.