BACKGROUND
Medullary thyroid cancer (MTC) is a relatively rare form of thyroid cancer. MTC arises from Parafollicular or C cells in the thyroid. These cells produce the hormone calcitonin and the cancer marker carcinoembryonic antigen (CEA). This is contrast to the far more common papillary and follicular cancers that arise from the thyroid follicular cells that make thyroid hormone. Calcitonin and CEA are used to follow treatment of MTC and persistent levels indicate persistent cancer cells. Further, the rate of increase of calcitonin, also known as doubling time, is helpful to determine prognosis using the International Medullary Thyroid Carcinoma Grading System. This system uses the characteristics of the cancer cells as well as the Ki67 protein, which is associated with cell growth.

The goal of this study was to determine the factors that help predict outcomes in small medullary thyroid cancers, also known as medullary microcarcinomas (<1 cm), as there studies that suggest they may have very different outcomes than larger cancers.

THE FULL ARTICLE TITLE
Kesby N et al. Natural history and predictive factors of outcome in medullary thyroid microcarcinoma. J Clin Endocrinol Metab 108:2626–2634. PMID: 36964913

SUMMARY OF THE STUDY
This study included patients with an MTC ≤1 cm treated surgically between 1995 and 2022 who were in a endocrine surgery database in Australia. Patients with hereditary diseases were excluded. Details of their surgery, the surgical specimen, follow-up clinical information, cancer markers, and imaging were collected. Prognostic factors included in this study were primary cancer size, cancer grade, spread to the lymph nodes and postoperative calcitonin levels. There were 42 patients for inclusion in the final analysis. The average age was 60 years.

Patients who had MTC <0.5 mm were less likely to have spread to the lymph nodes or to be high grade, compared to those with MTC 0.5 to 1 cm. Patients with high-grade MTC were more likely to have larger cancers, higher serum calcitonin levels, and spread to the lymph nodes than were those with low-grade cancers. The rate of recurrence for cancers <0.5 cm was not significantly different from that for cancers 0.5 to 1 cm. All low-grade cancers showed no risk of recurrence within 5 years, where as in high grade cancers, recurrences occurred within 5 years in 50% of cases. The prognosis was also worse for those with high grade MTC than for those with low-grade MTC. Recurrence was more common in patients with spread to the lymph nodes and survival was also worse than those with no spread to the lymph nodes. Increased postoperative calcitonin levels were associated with more cancer recurrence. The extent of thyroid surgery did not significantly affect recurrence risks.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Patients with small, low-grade MTC have very good outcomes, particularly if they achieve a normal postoperative calcitonin level. This study indicates that these patients will likely not need any further treatment and suggests that extensive follow-up after diagnosis may be unnecessary. It is very important for patients to understand the particular characteristics of their thyroid cancer that determine their prognosis so they can be engaged with their care plan and sensibly proceed with their decision-making. Thyroid cancers are NOT all created equal.

— Maria Brito, MD, ECNU

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