Abstract
The best strategy for the long-term follow-up of patients with differentiated thyroid carcinoma (DTC) after excellent response to initial therapy represents a challenge. These patients are not “cured” because late recurrences, while uncommon, may still occur. A balance is sought between the detection of these few cases of recurrence without imposing great cost on the majority of patients for whom follow-up would not result in any change of management (1). Currently, the cost of surveillance for DTC patients is unjustifiably greater for low-risk patients (1).
In a recent publication in this journal, Jeon et al. (2) evaluated the rate of structural recurrences and how they were detected in patients with DTC of low or intermediate risk who exhibited an excellent response to initial therapy. The results were apparently different from those reported previously by our group (3), as highlighted by the authors. Consequently, the follow-up recommended by Jeon et al. (fig. 2 [2]) differs from our proposal (3). According to these authors, repetitions (at certain periodic intervals) of serum thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) would still be necessary, even after documenting an excellent response to therapy (2), while we consider clinical examination and Tg measurement to be sufficient (3).
In the conclusion of our study, we emphasize that “our conclusions apply to (i) low- or intermediate-risk patients, (ii) who have undetectable TgAb and (iii) neck US performed by an experienced professional showing no abnormalities after initial therapy, and (iv) when Tg is measured with a second-generation assay” (3). Although the clinical impact is still controversial (4), it has been shown that borderline TgAb (i.e., below the reference range but detectable) can interfere with Tg concentrations (5). Thus, patients 4, 8, and 12 in table 2 in Jeon et al.'s article (2) do not fit within our proposal because they had borderline TgAb in the initial assessment and persisted with borderline TgAb at the time recurrence was detected in the absence of Tg elevation. Among patients with undetectable TgAb in the initial assessment, seven progressed to Tg elevation, structural disease was not detected in three, and US revealed lymph node metastases (LNM) in four (patients 9, 10, 11, and 13 of table 2 [2]). Our follow-up proposal would capture these last patients (3). Finally, among patients with an excellent response, considering here undetectable TgAb, who continued to have Tg <0.2 ng/mL, Jeon et al. (2) found six structural recurrences on US. We also detected one recurrence on US among 560 patients with the findings mentioned above (3). Thus, although the frequency is different, we recognize that a new US can detect recurrence, even in patients who continue with negative Tg during follow-up (3).
Based on this, we question the need to repeat US. Even based on the results of Jeon et al. (2), we estimate one recurrence in approximately 200 patients. If we consider that each patient undergoes only two additional US exams after evaluation that defined excellent response, we will have 400 US exams performed to detect one recurrence. We reiterate that we perform only two US exams per patient during follow-up in low and intermediate risk and excellent response to initial therapy. The cost of this management appears high (1). In our patient (3) and in the six patients of Jeon et al. (2) who had disease on US despite unstimulated Tg <0.2 ng/mL, LNM did not exceed 8 mm and were single in most patients. According to the American Thyroid Association guidelines (6), fine-needle aspiration and intervention are not necessary (recommendations 65 and 71). Thus, we doubt that outcomes will be significantly compromised if these LNM were not readily detected but the patients continued under follow-up as proposed by us, and if they were diagnosed when Tg elevation occurs or, more rarely, when these lymph nodes become palpable. Perhaps an acceptable compromise would be to repeat US on a single occasion, for example five years after excellent response to therapy is documented.
Finally, regarding the repetition of TgAb always when Tg is measured, in the series of Jeon et al. (2), the only patient who developed elevated TgAb titers already had borderline TgAb at the initial assessment and does not fit within our proposal (3). No disease was found in the remaining patients with elevated TgAb. Thus, the results of that study (2) do not support the value of periodic TgAb repetition for detecting recurrence in patients with excellent response to therapy and undetectable TgAb at initial assessment. This is particularly true for countries such as Brazil where Tg and TgAb are requested separately (as two separate tests). In this respect, our results (3) showed good concordance.
Although the non-suppression of TSH, non-repetition of stimulated Tg, and non-execution of whole-body scanning (2,3,6) are important advances in the follow-up of patients with excellent response to therapy, we advocate that follow-up be further simplified (3).
Footnotes
Author Disclosure Statement
No competing financial interests exist.