In patients with DTC, 131-radioiodine ablation of remnant functional thyroid tissue following (near)total thyroidectomy aims at reducing the risk of recurrence and/or mortality and at facilitating patients’ follow-up. However, because of the good prognosis of most DTC and of the possible risks associated with exposure to ionizing radiation, uncertainty has raised about the necessity of treating all DTC patients with 131I, as well as about the optimal amount of radioiodine required for effective ablation.
To address these issues, the American Thyroid Association (ATA) presented management guidelines in 2014, proposing a therapeutic approach for DTC in which postoperative staging based on pathology is recommended not only for assessing risk for recurrence and mortality, but also for tailoring decisions regarding the need for adjuvant therapy (1,2,4). The guidelines also put forward the use of rhTSH preparation instead of hormone suppression for low- and intermediate-risk patients.
Since the publication of these guidelines, a standardized therapeutic protocol is applied to all patients treated for DTC in our institution, consisting in no administration of 131-iodine after surgery in low-risk patients and a low activity even in high-risk patients except with known distant metastasis, as well as the (almost) systematic use of rhTSH before iodine treatment. The primary goal of the present study was to evaluate the effect of this management strategy for DTC on the rate of response to treatment and/or recurrence compared to the previous treatment policy. Furthermore, because local toxicity of RAI and duration of hospital stay are related to the amount of administered activity, and the treatment tolerance is influenced by the preparation regimen, our secondary goal was to analyze the effect of the changes in management strategy on these parameters.
Data in the literature are somehow contradictory with regard to the efficacy of low dose RAI after surgery in patients with DTC. A systematic review of randomized and observational studies published in 2007 was inconclusive as to whether low-dose 131-radioiodine (1.1GBq [30 mCi]) was associated with rates of ablation success similar to - or lower than - rates obtained with high-dose radioiodine (3.7 GBq [100 mCi]) (5). More recently, other researchers reported that high dose of 131I resulted in a successful ablation more often than low dose (3,6,12), especially in those patients with positive anti thyroglobulin antibodies or higher stimulated thyroglobulin levels at the moment of radioiodine ablation (12).
In our patients, the rate of complete response since 2015 did not differ significantly from the historical control group regardless of the risk stratification patients, despite a significant decrease in 131I activity and no RAI in low-risk patients. The same rate of complete response was achieved by administering 1.1GBq [30 mCi] instead of 3.7 GBq [100 mCi] in patients with DTC. These observations are in agreement with other studies, which used the ablation success rate as a surrogate clinical end point for response to 131I. Castagna et al. provided the first evidence that in DTC patients, high RAI activities at ablation had no major advantage over low activities (7). This was confirmed in a meta-analysis by Cheng et al. and large multicenter randomized trials (8-11,13,14), showing that low-dose radioiodine (1.1GBq [30 mCi]) is as effective as a high-dose (3.7 GBq [100 mCi]) in ablating thyroid remnant in patients with DTC.
The use of low RAI activity has several advantages for the patient as well as for the community. First, patients have fewer side effects, both immediate and delayed, including a reduced risk of developing another primary cancer due to the exposure to ionizing radiations (9).
Second, reducing the RAI activity is cost-effective. Shortening the duration of hospital stay, and even avoiding hospitalization in case of low-risk DTC, significantly reduces the financial costs incurred by the health service provider. In our study, median hospitalization was 3 days before 2015 and 1.5 days after. Third, the duration of compulsory isolation, homestay and social distancing after hospital discharge is also reduced, allowing patients to resume work and normal life more rapidly. Lastly, administration of a lower activity decreases the radioactive waste and exposure to the environment (9).
2015 was a key year for the management of DTC patients in our institution: besides the adoption of a therapeutic approach based on the risk of recurrence, preparation to RAI by rhTSH administration became the standard of care regardless of the risk assessment. Since 2015, 97.4% of the patients have received rhTSH (vs 23.4% before), with a very similar high rate of complete therapeutic response for the intermediate and even the high risk group. As expected, tolerance to treatment improved noticeably, with no reported side effects after rhTSH injection, vs in 1/3 of the patients after hormonal suppression, mostly related to hypothyroidism.
These observations confirm a recently published consensus paper stating that, in patients with ATA low- and intermediate-risks DTC without extensive lymph node involvement, and sometimes even in high-risk patients, preparation for RAI with rhTSH stimulation is an acceptable alternative to thyroid hormone withdrawal for achieving remnant ablation, based on evidence of superior short-term quality of life and noninferiority of remnant ablation efficacy (2).
The results of our study seem promising and may have important practical implications with regard to improvement of treatment, by making therapies safer and more convenient, with a higher quality of life. They sustain the personalized approach to treatment, follow-up and prognosis proposed by 2015 ATA guidelines.
However, their potential clinical impact is currently limited by the relatively small number of patients already included, the use of historical controls, with potential biases related to differences in surgical techniques or recommended standards of care as well as the chosen minimal duration of follow-up of 2 years. This duration is an intermediate period compared with other studies, maybe too short given the known slow progression of DTC. This number continues to increase and more follow-up data will be available for analysis in the future.