Long-term outcome of “prophylactic therapy” for familial medullary thyroid cancer

Background. About one quarter of all medullary thyroid cancers (MTC) are determined genetically due to a mutation in the RET prolo-oncogene. The most common site of mutation is in codon 634. Therapeutic approaches toward patients at, risk for the development of MTC identified by family screening programs range from total thyroidectomy to total thyroidectomy with lymphadenectomy of all 4 compartments. Methods. We report 17 patients (median age, 13 years; range, 4-36) carrying a mutation in codon 634 of the RET prolo-oncogene who were operated on prophylactically at our department. All patients underwent thyroidectomy with bilateral cervicocentral lymphadenectomy. Current calcitonin level, overall survival, and disease-free survival were analyzed by contacting general practitioners and patients. Results. Tumor classification was as follows: C-cell hyperplasia, 18% (n = 3); T1 (<1 cm), 71% (n = 12); and T1 (>1 cm), 12% (n = 2). Only 2 patients had lymph node metastases (12%). These patients developed recurrent disease (median observation lime, 147 months; range, 90-181). In 1 patient, the calcitonin level normalized after unilateral cervicolateral lymphadenectomy. The other patient (9 years old at primary operation) still has a persistently increased serum calcitonin Level after 140 months of follow-up despite several operations for MTC. Conclusion. Total thyroidectomy with bilateral cervicocentral lymphadenectomy is sufficient as routine "prophylactic therapy" for patients with mutations in codon 634 of the RE, T proto-oncogene. Cervicolateral lymphadenectomy is indicated if calcitonin remains elevated after primary surgery. Prophylactic thyroidectomy should be performed before the development of lymph node metastases. (Surgery 2009;146:906-12.)