We sought to assess whether extensive surgical treatment, postsurgical radioiodine therapy, or both decrease the risk of locoregional recurrence (LR) after curative primary treatment in children and adolescents diagnosed with differentiated thyroid cancer (DTC) at age ≤18 y. Methods: To determine the incidence of and identify predictive factors for thyroid bed recurrence (TBR) or lymph node recurrence (NR), we performed a chart review and retrospective multivariate Cox regression analysis on 235 patients with DTC diagnosed at age ≤18 y and managed with curative intent at our tertiary referral center from 1973 to 2002; 40 of these patients had distant metastases at diagnosis. We also determined overall and recurrence-free survival and generated curves for these variables using Kaplan–Meier and Cox univariate analysis. Results: During a median follow-up of 82 mo (range, 5–402 mo), no DTC-related deaths occurred, 203 (86%) children remained recurrence-free, and 32 (14%) children had LR, including TBR in 9 (28% of LR), NR in 20 (63% of LR), and both in 3 (9% of LR). Among patients treated with radical intent and showing no distant metastases, the most recent thyroglobulin level was <1 ng/mL in all but 4% of cases. The median time from the first surgery to LR was 37 mo (range, 9–280 mo). In multivariate analysis, significant risk factors for TBR were less than total thyroidectomy and lack of postsurgical radioiodine treatment (respective risk increases of 9.5 [P = 0.04] and 11 times [P = 0.03]). For NR, classic papillary histology, incomplete primary lymph node management (i.e., lack of modified lymphadenectomy of affected lymph nodes or lack of confirmation of disease-free nodes by intraoperative staging), and absence of adjuvant radioiodine therapy were independent significant predictive factors that increased the recurrence risk by 1.9 (P = 0.02), 3.3 (P = 0.02), and 3.2 (P = 0.02) times, respectively. Age or sex did not correlate with LR risk. Conclusion: In DTC patients ≤18 y of age, extensive initial therapy—consisting of total thyroidectomy combined with modified lymphadenectomy performed in case of lymph node metastases and followed by radioiodine therapy—is associated with a substantial decrease of DTC LR risk.

Well under 15% of differentiated thyroid carcinoma (DTC) is diagnosed at ≤18 years of age. The population is heterogenous and the differences between prepubertal children and pubertals and adolescents are to be considered. Although very little has been reported on children with sporadic DTC under the age of 10 years, juvenile DTC has at least some undeniable differences with adult DTC: (1) larger primary tumor at diagnosis; (2) metastatic pattern and features, namely: (a) greater prevalence of neck lymph node and distant metastases at diagnosis, (b) lungs almost the sole distant metastatic site, (c) pulmonary metastases nearly always functional; (3) closer-to-normal and more frequent sodium-iodide symporter (NIS) expression; and (4) higher recurrence rate but longer overall survival. These differences are especially distinct in prepubertal children. The goals of primary treatment of juvenile DTC are to eradicate disease and extend not only overall, but recurrence-free survival (RFS). Extending RFS is itself a desirable goal in children because it improves quality-of-life, alleviates anxiety during psychologically formative years, reduces medical resource consumption, and may increase overall survival. Primary treatment of DTC generally comprises a combination of surgery, radioiodine (¹³¹I) ablation, and thyroid hormone therapy applied at varying levels of intensity. Therapeutic decision-making must rely on retrospective adult and/or pediatric outcome studies and on treatment guidelines formulated mostly for adults. Differences between juvenile and adult DTC and physiology dictate distinct treatment strategies for children. We, and many others, advocate a routine intensive approach because of the more advanced disease at diagnosis, propensity for recurrence, and greater radioiodine responsiveness in children, as well as published evidence of significant survival benefits, especially regarding RFS. This intensive approach consists of total thyroidectomy and central lymphadenectomy in all cases, completed by modified lateral lymphadenectomy when necessary and followed by radioiodine administration. However, absence of prospective studies and of universal proof of overall cause-specific survival benefits of this approach have led some to propose more conservative strategies. Most European centers give radioiodine ablation to the vast majority of juvenile DTC patients. Ablation seeks to destroy any residual cancer, including microfoci, as well as healthy thyroid remnant. Large studies have documented the procedure to decrease cause-specific death rates and, in children, to significantly lessen locoregional recurrence rates (by factors of 2–11) independent of the extent of surgery. There is universal agreement on treating inoperable functional metastases with large radioiodine activities. Treatment is especially effective in small tumor foci up to 1 cm in diameter, and should be administered every 6–12 months until complete response, loss of functionality, or attainment of cumulative activities between 18.5–37GBq (500–1000 mCi). Radioiodine therapy is generally safe. Short-term side effects include nausea and vomiting (more frequent in children than in adults), transient neck pain and edema, sialadenitis (<5% incidence), mild myelosuppression (~25%), transient impairment of gonadal function both in females and males (sperm quality in boys), or nasolacrimal obstruction (~3%), with most cases generally being asymptomatic–moderate, self-limiting, or easily prevented or treated. If pregnancy is ruled out before each ¹³¹I administration, and conception avoided in the year afterward, radioiodine therapy appears not to impair fertility. However, therapeutic ¹³¹I carries a small but definite increase in cancer risk, particularly in the salivary glands, colon, rectum, soft tissue and bone. To better guide primary treatment, different therapeutic combinations should be prospectively compared using RFS as the primary endpoint. Efforts also should be made to identify molecular signatures predicting recurrence, metastasis and mortality.

Background: The American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer (DTC) are highly influential practice recommendations. The latest revision appeared in 2015 (“ATA 2015”). These guidelines were developed predominantly by North American experts. European experts frequently have different perspectives, given epidemiological, technological/methodological, practice organization, and medicolegal differences between the respective regions. Summary: Divergent viewpoints were the focus of an invited symposium organized by the European Association of Nuclear Medicine involving 17 European thyroidologists, 4 ATA Guidelines Taskforce members, and an audience of 200 international experts. The group discussed “preoperative assessment of thyroid nodules,” “surgery and role of pathology,” “radioiodine therapy (RAIT),” “assessment of initial therapy and dynamic risk stratification,” and “treatment of persistent disease, recurrences, and advanced thyroid cancer.” The dialogue resulted in this position paper contrasting European and ATA 2015 perspectives on key issues. One difference pertains to ATA 2015’s permissiveness of lobectomy for primary tumors ≤4 cm. European panelists cited preclusion of RAIT, potential need for completion thyroidectomy, frequent inability to avoid chronic thyroid hormone replacement, and limitations of supportive evidence as arguments against widely applying lobectomy. Significant divergence involved ATA 2015’s guidance regarding RAIT. European panelists favored wider use of post-operative RAIT than does ATA 2015. Rationales included the modality’s association with favorable patient outcomes and generally limited toxicity, and lack of high-quality evidence supporting withholding RAIT. Additionally, European panelists favored recombinant human thyrotropin in more settings than does ATA 2015, citing avoidance of hypothyroid morbidity and quality-of-life impairment, without apparent sacrifice in oncologic outcomes. Based on clinicial evidence plus theoretical advantages, European experts advocated dosimetric versus fixed-activity RAIT approaches for advanced DTC. European panelists noted that the ATA 2015 risk stratification system requires information sometimes unavailable in everyday practice. ATA 2015 recommendations regarding radioiodine-refractory DTC should consider potential palliative benefits of RAIT in patients who also have radioiodine-susceptible lesions. Conclusions: European panelists suggested modifications to approximately one-third of ATA 2015 recommendations. Varying European and ATA 2015 perspectives can stimulate analysis and discussion of literature and performance of primary research to resolve discrepant recommendations and potentially improve patient outcomes.