Natural history, predictive factors of apparent disease (structural or biochemical) and spontaneous excellent response in patients with papillary thyroid carcinoma and indeterminate response to initial therapy with radioiodine

Abstract

Background: About 20% of patients with papillary thyroid carcinoma (PTC) submitted to total thyroidectomy followed by radioactive iodine (RAI) exhibit an indeterminate response to therapy. The aim was to evaluate the natural history, predictive factors of apparent disease (structural or biochemical), and spontaneous excellent response in patients with PTC and an initial indeterminate response to RAI therapy defined based on unstimulated Tg (u-Tg).

Methods: We evaluated 164 patients who were initially treated with total thyroidectomy and RAI and who had an indeterminate response to therapy (u-Tg between 0.2 and 1 ng/ml, undetectable anti-Tg antibodies [TgAb], and neck ultrasonography [US] without anomalies). None of the patients received empirical therapy with RAI. The patients were followed up for 24 to 144 months (median 72 months).

Results: Apparent disease occurred in 16 patients (9.7%), including 13 with structural disease and 3 with u-Tg elevation > 1 ng/ml, but no tumor was detected by the imaging methods (biochemical disease). A higher frequency of disease was observed in patients with >3 lymph node metastases (LNM) and initial u-Tg >0.35 ng/ml. The frequency was only 2% among patients with ≤3 LNM and u-Tg ≤0.35 ng/ml and 9.7% among patients with > 3 LNM or u-Tg >0.35 ng/ml, while the frequency was 27% in patients with >3 LNM and u-Tg >0.35 ng/ml. In the absence of any additional therapy, u-Tg was <0.2 ng/ml (excellent response) in the last assessment in 70 patients (42.7%). Only initial u-Tg was associated with a higher probability of spontaneously achieving an excellent response: 40/72 patients (55.5%) with u-Tg ≤0.35 ng/ml versus 30/92 patients (32.6%) with u-Tg >0.35 ng/ml.

Conclusions: A minority of patients with PTC and an initial indeterminate response to RAI defined based on u-Tg develop apparent disease (structural or biochemical) and many spontaneously achieve an excellent response. The risk of disease can be refined based on parameters such as the extent of lymph node involvement and initial Tg concentration.

Keywords: Apparent Disease; Indeterminate Response; Papillary Thyroid Carcinoma; Thyroglobulin.