Prophylactic and Early Thyroidectomy in RET Germline Mutation Carriers in Pediatric and Adult Population: Long-Term Outcomes of a Series of 63 Patients

Simple Summary Approximately 20% of medullary thyroid cancers (MTC) are hereditary and caused by specific germline RET protooncogene mutations. Screening for germline mutation in all newly identified cases and their relatives allows early or even prophylactic surgical treatment. The aim of this retrospective study was to assess the clinical features of RET mutation carriers according to the age at surgery and the long-term outcome in term of morbidity and recurrence rate after prophylactic and early thyroidectomy. The results demonstrated that prophylactic and early thyroidectomy are safe and effective procedures in achieving the cure; however, while patients with only C-cell hyperplasia are disease-free, patients with MTC, even when small and confined to the gland, could have recurrent disease at long-term. This finding suggest that prophylactic surgery should be performed earlier. Prophylactic and early thyroidectomy in RET germline mutation carriers allows the removal of the thyroid before medullary thyroid carcinoma (MTC) develops, or while it is still confined to the gland. This study was aimed to assess the clinicopathological features in RET carriers according to the age at surgery and the long-term outcomes after prophylactic and early thyroidectomy. A retrospective analysis of 63 operated asymptomatic RET carriers diagnosed after familial genetic screening was performed. Twenty-one RET carriers were operated at pediatric (<18 yrs) and 42 at adult (>= 18 yrs) age. Serum preoperative calcitonin levels were significantly lower in pediatric compared to adult patients (p = 0.04); moreover, adult RET carriers had a greater frequency of microMTC at pathology (p = 0.009). Permanent postoperative morbidity occurred in 9.5% of patients, without differences between the two groups. Biochemical postoperative cure was achieved in all patients. At a median follow-up of 14 years, all C-cell hyperplasia patients are disease-free; conversely, biochemical, and structural recurrence of disease occurred in three adults and one pediatric patient with microMTC. The independent predictive factors of MTC were the age at surgery, the preoperative calcitonin level and the RET mutational risk profile (p < 0.02). In conclusion, prophylactic and early thyroidectomy are safe and effective procedures in achieving definitive cure in most RET carriers. However, since recurrences may occur at long-term in case of microMTC, thyroidectomy should be possibly performed earlier to prevent microMTC development.