Current Controversies in the Management of Pediatric Patients with Well-Differentiated Nonmedullary Thyroid Cancer: A Review

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Abstract
Current treatment strategies for pediatric patients with nonmedullary, well-differentiated thyroid carcinoma (WDTC) are derived from single-institution clinical cohorts, reports of extensive personal experience, and extrapolation of several common therapeutic practices for this tumor in adults. Because pediatric WDTC is an uncommon malignancy, the issues of its optimal initial and subsequent long-term treatment and follow-up remain controversial. Pediatric patients with WDTC can be divided into two groups: children younger than 10 years of age and teenagers/adolescents between 10 and 18 years of age because these groups have different recurrence and mortality rates. We hereby present our views and interpret them in the light of the pertinent literature. Our recommendations on treatment strategies are more relevant for younger children. After midpuberty, optimal treatment is adequately addressed in the relevant literature on adults. For the majority of patients, total/near-total thyroidectomy is currently recommended as the standard initial therapy for WDTC. This is commonly followed by administration of radioiodine (RAI; 131I) therapy to destroy residual normal thyroid tissue (remnant). Routine 131I remnant ablation has been shown to: (1). decrease the risk of local recurrences, (2) increase the sensitivity of subsequent diagnostic RAI whole-body scanning (WBS), and (3) render serum thyroglobulin (Tg) a highly sensitive marker for recurrent/residual disease during long-term follow-up. We recognize that the above practices are not universally adhered to in children and adolescents, because the risk stratification and intensity of applied therapeutic measures are influenced by institutional traditions and personal experience. In our view, aggressive initial management, followed by evaluations at regular intervals after thyroidectomy and 131I remnant ablation, in conjunction with long-term thyroid hormone suppressive therapy (THST), result in decreased recurrence rates in pediatric patients with WDTC. Follow-up examinations should include a diagnostic RAI (131I or 123I) WBS and measurement of serum Tg, both performed under conditions of TSH stimulation, as well as neck ultrasonography (US). Our strategy is corroborated by data from retrospective clinical cohort studies. In this malignancy, no evidence of disease (NED) status can be defined as the combination of a negative diagnostic WBS and the presence of undetectable or low serum Tg levels, both tested under TSH stimulation. These findings should be accompanied by the absence of anatomically definable disease by standard imaging modalities, e.g., neck US or chest computed tomography (CT). Although the long-term survival rates are good overall in this disease, selected patients may require further surgery or 131I therapy for the eradication or clinical control of metastases. Finally, and importantly, because the duration of follow-up is lifelong, the care of children with prior diagnosis of WDTC should be transferred to an adult endocrinologist after they reach adulthood, even if they have achieved NED status by that time.