BACKGROUND
Medullary thyroid carcinoma (MTC) is a rare thyroid cancer that originates from cells called parafollicular cells in the thyroid that produce a hormone called calcitonin. Calcitonin plays a minor role in the regulation of the body’s calcium levels. In the setting of MTC, calcitonin serves as a cancer marker, since the cancer cells continue to secrete calcitonin. After surgery for MTC, calcitonin levels that fall to undetectable indicate a complete response to the surgery while persistent measurable calcitonin levels likely indicate persistent cancer cells. Further, increasing calcitonin levels after initial treatment usually indicates progression and growth of remaining cancer cells. Calcitonin levels can also help guide surgery in patients initially diagnosed with MTC. The American Thyroid Association guidelines for management of MTC indicate that when a calcitonin level is more than 500 pg/ml prior to thyroid surgery it is recommended to perform more imaging to rule out spread of the cancer outside of the neck. That said, there is controversy regarding the best cutoff calcitonin level to identify cancer that has spread outside of the neck as opposed to cancer limited to the thyroid and local lymph nodes. In addition, there is debate about the extent of surgery in the neck in patients who do not have known spread of the cancer outside of the thyroid prior to surgery.

This study was done to determine the which factors are associated with MTC response after surgery, cancer recurrence and effective treatment without the cancer progressing (progression-free survival, PFS).

THE FULL ARTICLE TITLE
Abou Azar S et al. Medullary thyroid cancer: single institute experience over 3 decades and risk factors for recurrence. J Clin Endocrinol Metab 2024;109(11):2729- 2734; doi: 10.1210/clinem/dgae279. PMID: 38651609.

SUMMARY OF THE STUDY
This study looked at patients with MTC treated at the University of Chicago between 1990 and 2023. A total of 68 patients with MTC were included. The average age at diagnosis was 54.9 years, 44 (65%) were female. During the preoperative workup, 16 patients (24%) were found to have cancer spread to the lateral neck and 3 (4%) patients had spread outside of the neck. Preoperative calcitonin levels were documented in 56 patients, and the average calcitonin level was 504.4 pg/ ml. Of these patients, 10 had their thyroid removed (total thyroidectomy), 28 had their thyroids removed along with lymph nodes in the central part of the neck (total thyroidectomy + central neck dissection), 17 had their thyroids, central lymph nodes removed and lymph nodes either the right or left side of their neck removed (unilateral lateral neck dissection), and 8 patients had a total thyroidectomy, central neck dissection and bilateral neck dissection.

Beyond 1 year after initial surgery, 4% died and 22% had recurrence, with an average age of 4.7 years. Overall 9 patients (13.2%) had a recurrence in the neck, and 6 (8.8%) had a recurrence outside the neck. Reoperation was performed in 10 patients (15%) and 11 (16%) underwent systemic treatment and/or palliative radiation therapy. Patients with cancer recurrence were more likely to be men, have had more lateral neck lymph nodes involved on the initial surgery and had more high-risk mutations within the cancer cells. Further, a calcitonin level >2175 pg/ml prior to surgery was a strong predictor for spread of the cancer outside of the neck and a good predictor of spread of the cancer to the lateral neck.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study showed that the extent of surgery is not associated with the risk of recurrence and that the calcitonin level may be quite high even in patients who do not have spread of the cancer outside of the neck. This study is limited by the small number of patients. This study is important because clinical practice and guidelines will change over time if there is no benefit to more aggressive surgery for patients. It is also important for patients to know that even though they may need a workup to rule out spread of the cancer outside of the neck due to a high calcitonin level, it is possible that the cancer may still only be localized in the neck.

— Maria Brito, MD, ECNU

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