Compartment-Specific Recurrence in Medullary Thyroid Cancer.

Abstract

Total thyroidectomy with bilateral central neck dissection is recommended for medullary thyroid carcinoma (MTC), even in patients without clinical nodal involvement. However, the role of contralateral prophylactic central neck dissection (pCND) remains debated, leading to variations in practice. To evaluate the outcomes of nodal dissection in compartment-specific recurrence in patients undergoing surgical treatment for MTC, including a subgroup analysis of patients with preoperative clinically node-negative (cN0) disease stratified by whether they underwent contralateral pCND. This was a multicenter retrospective cohort study of adult patients with MTC who underwent thyroidectomy between 1998 and 2021 in 4 academic referral centers. Data were analyzed from February to July 2026. Patients with missing operative data, including initial thyroidectomy information and central neck dissection laterality, were excluded. Contralateral pCND at the time of initial surgical treatment. Recurrence categorized as biochemical (calcitonin >2 pg/mL without radiographic findings); ipsilateral central, ipsilateral lateral, contralateral central, and contralateral lateral neck; and distant metastatic. Effect size was reported as Rosenthal r (r) for continuous variables and as risk difference (RD) with 95% CIs for categorical variables. Multivariable Cox regression was used to evaluate risk factors for contralateral neck recurrence and overall recurrence. This study in a total of 235 patients who underwent surgical treatment for MTC (132 [56%] female; median age, 56 years [IQR, 43-66 years]) found that, preoperatively, 105 patients (45%) had cN0 disease, of whom 58 (55%) underwent contralateral pCND. Genetic testing was performed in 127 (54%) patients, with a 25% rate of germline RET variant. Overall, 73 patients (31%) developed disease recurrence: 15% in the ipsilateral central, 15% ipsilateral lateral, 5% contralateral central, and 8% contralateral lateral neck; 11% distant metastatic; and 4% biochemical. Among patients with cN0 disease, differences in the rates of overall recurrence (22% vs 15%; RD, 0.07; 95% CI, -0.07 to 0.22) and contralateral central neck recurrence (5% vs 2%; RD, 0.03; 95% CI, -0.04 to 0.10) were small and imprecisely estimated between those who did and did not undergo contralateral pCND. On multivariable analysis adjusting for sex, tumor size, and nodal involvement, contralateral pCND was not associated with reduced overall recurrence (hazard ratio [HR], 0.59; 95% CI, 0.21-1.62) or contralateral neck recurrence (HR, 0.23; 95% CI, 0.02-3.08). This study found that, in MTC, the most frequent sites of recurrence were the ipsilateral central and lateral neck. Contralateral central neck recurrence was uncommon; however, our wide CIs preclude definitive conclusions about the benefit of contralateral pCND, and larger studies are warranted.