Patterns of Recurrence in Medullary Thyroid Cancer: A Multi-institutional Retrospective Study

Young-Ji Seo1, Kelsy N Larios1, Yifan Mao1, Yehia Elkersh2, Bryce England3, Elena G Hughes1, Masha J Livhits1, Michael W Yeh1, Trevor Angell4, Lina Hu3, Denise Lee2, James X Wu1.

1. Section of Endocrine Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA
2. Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 
3. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
4. Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, CA, 

Background: The recommended operation for medullary thyroid carcinoma (MTC) is total thyroidectomy with bilateral central neck dissection, even in patients without clinical nodal involvement. However, the role of contralateral prophylactic central neck dissection (pCND) remains debated, leading to variations in practice. We evaluated recurrence patterns in MTC and the impact of nodal dissection on compartment-specific recurrence.

Methods: We conducted a retrospective cohort study across four academic centers of 266 patients who underwent surgery for MTC (1998–2021), excluding those with missing operative details. Recurrences were categorized as biochemical (calcitonin >2 ng/L without radiographic findings), ipsilateral central, ipsilateral lateral, contralateral central, contralateral lateral, and distant metastasis. A subgroup analysis of patients with preoperative cN0 disease was performed, stratified by whether they underwent contralateral pCND, with recurrence assessed by compartment. Multivariable logistic regression was used to evaluate risk factors for contralateral neck recurrence.

Results: The final cohort included 235 patients (56% female; median age 56), of whom 58% underwent genetic testing and 25% had a germline RET mutation. Preoperatively, 105 (45%) had cN0 disease, 98 (42%) had cN1 disease, and 32 (13%) lacked preoperative imaging. Overall, 73 patients (31%) developed disease recurrence: 15% in the ipsilateral central neck, 15% ipsilateral lateral, 5% contralateral central, 8% contralateral lateral, 11% distant metastases, and 4% biochemical. Among the 105 cN0 patients, of which 58 (53%) underwent contralateral pCND, contralateral central and lateral neck recurrences occurred in 4% and 6%, respectively. Rates of contralateral central neck recurrence were similar between those who did and did not undergo pCND (7% vs. 4%, p=0.56). On multivariable analysis adjusting for sex, tumor size, and nodal involvement, contralateral pCND was not associated with reduced overall recurrence (OR 0.83, 95% CI 0.24–2.91, p=0.77) or contralateral neck recurrence (OR 1.01, 95% CI 0.15–6.96, p=0.99).

Conclusion: In MTC, the most frequent recurrence sites are the ipsilateral central and lateral neck. Contralateral central neck recurrence is uncommon, and pCND did not reduce recurrence in cN0 patients. Prospective trials should assess unilateral surgery in select cases.