Background: Data on long term outcomes of patients with differentiated thyroid cancer (DTC) with indeterminate response to initial treatment (IR) is lacking. Objective: a) to assess long term outcomes of patients with IR, b) to describe differences in evolution according to type of IR positive anti-thyroglobulin antibodies (TgAb) vs positive thyroglobulin (Tg) and c) to determine factors related to worse prognosis in this population Patients and methods: Retrospective study of 58 DTC patients with IR after total thyroidectomy and radioiodine ablation. Population was divided in two groups: TgAb (+) and Tg (+). Results: After a median follow-up of 6.2 years, structural disease was found in 3.4% of cases, all of them in the Tg (+) group. Final IR were more frequent in the TgAb (+) group (75% vs 23% in the Tg (+) group, p <0.0005), they were caused by declining TgAb levels in 83% of cases. Patients with final excellent and IR had smaller tumor at diagnosis (11.5 vs 44.4 mm, p 0.03), initial high risk was less frequent (14.8 vs 60%, p 0.02), and preablation Tg levels were lower (10.1 vs 42.9 ng/ml, p 0.03) compared with patients with structural or biochemical persistence. Conclusions: Most patients with IR had favorable outcomes. Structural disease was found only in patients with Tg (+). Patients with worse final outcomes had adverse initial parameters. Management strategies should be tailored according to these findings. Significance Statement: Our objective was to evaluate the long-term evolution of patients with an indeterminate response to initial treatment, to investigate differences in the final state between the different types of indeterminate response (positive antithyroglobulin antibodies vs. detectable thyroglobulin), and to determine factors that are associated with worse evolution in this population. We found it relevant to study this population given the little evidence published to date on this group of patients.

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