Prospective Trial of Unilateral Surgery for Nonhereditary Medullary Thyroid Carcinoma in Patients without Germline RET Mutations

Abstract

Although sporadic medullary thyroid carcinoma (MTC) tends to be unicentric and confined to one lobe, total thyroidectomy is usually performed because of the risk of a hereditary or bilateral process. Germline RET mutation analysis can discriminate hereditary MTC and truly sporadic, nonhereditary MTC. We analyzed 72 of 94 patients with MTC to establish the genetic nature and the clinical features of nonhereditary MTC. Since 1996 we have prospectively treated 15 patients with nonhereditary MTC (prospective study group, or PSG) according to a unilateral surgery policy. A group of 22 previously operated patients in whom the nonhereditary nature was established served as controls (retrospective study group, or RSG). Systematic central and ipsilateral neck dissection was performed in both groups. Outcome was assessed using postoperative stimulated serum calcitonin levels; a normal value was considered a biochemical cure. All 24 hereditary MTC patients carried germline RET mutations: 8 of 48 patients with apparently sporadic MTC had the mutations, and 6 of the 8 had bilateral MTC. All 40 patients without mutations had a unilateral tumor. In the RSG group 15 of 22 (68%) patients underwent total thyroidectomy, and the biochemical cure rate was 68%. Although only 3 of 15 (20%) of the PSG patients underwent total thyroidectomy, 12 of the 15 (80%) achieved biochemical cure. Univariate analyses revealed that pathologic node involvement- high T and N stages-was adversely related to biochemical cure. The extent of thyroid resection was not related to biochemical cure. Of 20 patients with node involvement, 10 achieved biochemical cure, indicating the importance of systematic neck dissection. Hemithyroidectomy with systematic central and ipsilateral neck dissection is appropriate surgery for nonhereditary MTC.

Multiple endocrine neoplasia type 2

“…Calcitonin values (basal or stimulated by pentagastrin, calcium, or both) are nearly always elevated with MTC. Similarly, an elevated calcitonin level after surgery is thought to be the first sign of persistent, recurrent or generalized disease [7,43].…”

Surgical management of sporadic medullary thyroid cancer

“…Multivariable analysis by Pelizzo et al [7] has shown that total thyroidectomy was correlated with better survival and that the few cases of prolonged disease-free survival after isthmolobectomy were not sufficient to justify anything less than total thyroidectomy because of the limited number of patients [18].…”

Medullary Thyroid Carcinoma – Update and Present Management Controversies

“…14 However, in spite of these observations, it has been argued that when pre-operative mutational analysis has shown no RET germline mutation there may be a case for performing only hemithyroidectomy and isthmusectomy. In a group of highly selected patients with sporadic tumours, Miyauchi and colleagues 15 were able to demonstrate that successful outcome and biochemical cure with a normal postoperative calcitonin level were not compromised by performing unilateral resection. However, 18.3% of their series had intraglandular metastatic spread but these were all cases noted to have extensive nodal metastases.…”