Histology is More Ιmportant than Persistent Anti‐Tg antibodies for Progression of Differentiated Thyroid Cancer

CONTEXT Anti-thyroglobulin antibodies (anti-Tg), present in 20-25% of differentiated thyroid cancer (DTC) patients, interfere with thyroglobulin measurements posing a challenge in the follow-up. OBJECTIVES Aim of this study was to identify clinical-histological factors that may affect anti-Tg persistence and disease outcome in DTC with positive anti-Tg. METHODS We retrospectively studied 234 DTC patients, with positive anti-Tg at diagnosis (females: 82.1%, age at diagnosis: 46.0±14.4yrs, median follow-up: 5yrs (1.5-32yrs). 221/234(94.4%) received radioiodine (RAI) ablation. Patients were divided into two subgroups: those whose anti-Tg became undetectable (anti-Tg-NEG) and those whose anti-Tg remained positive (anti-Tg-POS) at the end of the follow-up period. RESULTS Anti-Tg-POS patients (n=80, 34.2%) compared to anti-Tg-NEG (n=154, 65.8%) had more frequently lymph-node infiltration (36.3% vs 20.1%, p=0.01), extrathyroidal extension (ETE, 35.0% vs 22.1%, p=0.04), poorly-differentiated-DTC and increased tumor size (p≤0.004). They received higher total RAI dose (p<0.001). In most cases, additional RAI-administration and/or additional surgeries did not lead to anti-Tg elimination. These had more frequently structural disease persistence/progression compared to anti-Tg-NEG (remission: 78.8% vs 95.5%, persistence: 13.8% vs 3.9%, progression: 7.5% vs 0.6%, p<0.001). In Kaplan Meier analysis the probability of disease progression was higher in anti-Tg-POS. In Cox-proportional-hazard analysis the predictors of disease progression were size (p=0.002) and ETE (p=0.006). CONCLUSIONS Worse histological features are more frequent in patients with anti-Tg persistence during follow-up. Further additional RAI-administration and/or surgeries do not affect anti-Tg elimination in most cases. Anti-Tg persistence correlates with structural persistence although tumor size and extrathyroidal extension are the main predictors of disease progression.