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Predictors of outcomes in patients with medullary thyroid cancer

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Medullary thyroid cancer (MTC) is a relatively rare type of thyroid cancer. While it is the 3rd most common type of thyroid cancer, it only comprises ~3% of all cases of thyroid cancer. MTC arises from the parafollicular cells of the thyroid, also known as C cells, which are responsible for producing the hormone calcitonin. The standard treatment for this cancer is removing the thyroid completely (total thyroidectomy) as well as the lymph nodes in the lateral neck (bilateral neck dissection). This treatment is considered the most effective way to cure the disease when it has not spread.

After surgery, physicians monitor for MTC recurrence by measuring serum calcitonin levels and performing imaging, most often neck ultrasound. If the cancer has been completely removed, calcitonin levels should be very low or undetectable. Undetectable calcitonin levels with negative neck imaging is evidence of a cure of MTC. For patients who are not cured, calcitonin levels steadily increase over time. Indeed, studies show that the long-term prognosis of MTC, the prediction of the course of the disease and the effectiveness of treatment depends on the rate at which the calcitonin level doubles (called the calcitonin doubling time (CDT). When the CDT is longer than two (2) years, overall survival, recurrence-free survival, and distant metastasis- free survival are significantly better.

Determining the grade of a cancer is also essential for predicting the prognosis. Cancer’s grade reflects how abnormal the cancer cells appear when examined under a microscope compared to normal cells. Cancers with cells closely resembling normal healthy cells are categorized as low-grade, while those with more abnormal cells are classified as high-grade. Low-grade cancers are usually less aggressive and have a better prognosis. The International Medullary Thyroid Cancer System is a recent development that measures the grade of MTC and utilizes three different markers of cell division. High levels of these markers indicate a high-grade cancer.

This study aimed to investigate the differences in CDT between high and low-grade MTC. The authors hypothesized that high-grade cancers would have a faster CDT, leading to a worse clinical outcomes.

Nigam A et al 2022. Tumor grade predicts for calcitonin doubling times and disease-specific outcomes after resection of medullary thyroid carcinoma. Thyroid 32:1193–1200. PMID: 35950622.

In this study, the authors investigated 117 patients who had undergone surgery for MTC between 1986 and 2017. Two pathologists evaluated the cancers and classified them as high or low grade based on the International Medullary Thyroid Cancer Scoring System. The patients’ serum calcitonin levels were measured before and after surgery, at 6 and 12 months post-surgery, and every 6 months after that.

The analysis revealed that cancer grade and CDT were powerful indicators of clinical outcomes. By the end of the study, 70.5% of patients with low-grade MTC remained cancer-free, whereas only 9.1% of high-grade MTC patients remained cancer-free. Additionally, 2.1% of low-grade MTC patients died, compared to 45.4% of high-grade MTC patients. Among the 95 patients with low-grade MTC, 6 (6.3%) had a CDT of 1-2 years, 23 (24%) had a CDT of 2 or more years, and 65 (68.4%) did not experience a doubling of calcitonin levels. But of the 22 patients with high-grade MTC, 16 (72.7%) had a CDT of 1 year or less, 4 (18.2%) had a CDT of 1-2 years, and only 1 patient did not experience a doubling of calcitonin levels. Thus, high-grade MTC patients had significantly faster CDT than low-grade MTC patients. Furthermore, patients with high-grade MTC and CDT of less than 2 years had the poorest overall survival and recurrence-free survival.

Cancer grade and CDT can help predict prognosis in MTC. Most patients with high-grade MTC have a CDT of less than 2 years. This is why it is essential to frequently monitor calcitonin levels in MTC survivors since a rapid doubling of levels may predict cancer recurrence.

— Phillip Segal, MD


Medullary thyroid cancer: a relatively rare type of thyroid cancer that often runs in families. Medullary cancer arises from the C-cells in the thyroid.

Bilateral Neck Dissection: Surgical removal of lymph node on both sides of the neck. This is done for cancers that are very likely to spread or have already spread to one or both sides of the neck.

Calcitonin: a hormone that is secreted by cells in the thyroid (C-cells) that has a minor effect on blood calcium levels. Calcitonin levels are increased in patients with medullary thyroid cancer.

Calcitonin doubling time (CDT): the rate at which the calcitonin level doubles, usually reported in years. The CDT is related to prognosis in medullary thyroid cancer.

Recurrence-free survival: the period of time during which a person with cancer remains free of any signs or symptoms of cancer recurrence in the area surrounding the original site of the tumor and the nearby lymph nodes.

Distant metastasis-free survival: the period of time during which a person with cancer remains free of any signs or symptoms of cancer recurrence in organs or tissues that are located far away from the original site of the cancer.