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THYROID CANCER
Calcitonin assay variability and surgical decision-making in medullary thyroid carcinoma
BACKGROUND
Medullary thyroid cancer (MTC) is a rare type of thyroid cancer arising from C-cells in the thyroid, which produce and release into the bloodstream a hormone named calcitonin (CT). In MTC, blood CT levels correlate closely with the cancer size and spread outside the thyroid in the neck lymph nodes and other distant organs. Therefore, it can be used to guide the extent of the initial surgery. The 2015 American Thyroid Association (ATA) guidelines make recommendations that the extent of the initial thyroid surgery should be based on blood CT levels, as an indication of neck lymph node involvement. However, older CT assays, such as the immunoradiometric assay were in use at that time. At present, more sensitive assays, such as chemiluminescence or electrochemiluminescence immunoassays, are the standard for blood CT measurement.
The goal of this study is to update the blood CT cutoff values for predicting the extent of spread of the cancer to the neck lymph node using the newer CT assays and to help determine the best operation for patients with MTC.
THE FULL ARTICLE TITLE
Du Y, et al. Updated thresholds of basal calcitonin level and extent of lymph node metastasis in initially treated medullary thyroid cancer. JAMA Otolaryngol Head Neck Surg 2025;151(8):761-767; doi: 10.1001/ jamaoto.2025.0542. PMID: 40569620.
SUMMARY OF THE STUDY
This multicenter study included 509 patients with newly diagnosed MTC without spread of the cancer outside of the neck who underwent initial surgical treatment at 13 Chinese hospitals between 2011 and 2024. All patients had a preoperative baseline blood CT test measured by the newer CT assays. The patients were categorized into 4 groups based on the extent of spread to the neck lymph nodes (lymph node metastasis, LNM): no LNM, LNM in the central neck, LMN in the lateral neck and LMN in the upper chest.
All patients underwent central neck lymph node removal. LNM outside of the central neck was done only if abnormal nodes were noted before surgery. The main study outcome was recurrence-free survival, defined as the duration from initial surgery to the first recurrence of the cancer. The 509 study patients were randomly assigned to either the training group (used to establish the serum CT levels predictive of spread of the MTC outside of the neck, 339 patients) or the validation group (testing the new CT levels for surgery, 170 patients) groups.
Out of the 509 study patients, 55% were females. The average patient age was 50 years, and the average follow-up was 52 months. There was a positive correlation between blood CT levels and the extent of neck LNM, with average CT values of 212 pg/ml in the no spread group, 468 pg/ml in the LNM in the central neck group, 1748 pg/ml in the LNM in the lateral neck, and 4558 pg/ml in the LNM in the upper chest group. Using the training group, the CT thresholds to predict the extent of neck LNM were calculated as being 242 pg/ ml for LNM in the central neck, 694 pg/ml for LNM in the lateral neck on 1 side, 2379 pg/ml for LNM in the lateral neck on both sides, and 2782 pg/ml for LNM in the upper chest. These new blood CT thresholds were superior compared to the thresholds used in the 2015 ATA guidelines to predict the extent of LNM in both the training and validation groups. The new CT thresholds were also superior in indicating the patients’ prognosis measured as recurrence-free survival in the 4 LNM groups. The 5-year recurrence-free survival was 95% in the no LNM, 93% in the LNM in the lateral neck on one side, 84% in the LNM in the lateral neck on both sides, and 73% in the LMN in the upper chest.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The study provides updated calcitonin thresholds using modern assays to predict neck LNM extent and recurrence risk in MTC. These thresholds can help decide the extent of initial surgery in MTC, and especially whether lateral neck dissection would be indicated. The results need to be validated in prospective studies in different populations.
— Alina Gavrila, MD, MMSC
ATA RESOURCES
Thyroid Cancer (Medullary): https://www.thyroid.org/medullary-thyroid-cancer/
ABBREVIATIONS & DEFINITIONS
Medullary thyroid cancer: a relatively rare type of thyroid cancer that often runs in families. Medullary cancer arises from the C-cells (parafollicular cells) in the thyroid.
Calcitonin: a hormone 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.
Central neck compartment: the central portion of the neck between the hyoid bone above, and the sternum and collar bones below and laterally limited by the carotid arteries.
Lateral neck compartment: the lateral portion of the neck lying outside the carotid arteries. Ipsilateral: on the same side of the neck where the thyroid cancer grows. Contralateral: on the opposite side of the neck compared to the thyroid cancer location. Bilateral: on both sides of the neck.
Lymph node: bean-shaped organ that plays a role in removing what the body considers harmful, such as infections and cancer cells.
Cancer metastasis: spread of cancer from the initial organ where it developed to other organs, such as the lungs and bone.
Cancer recurrence: this occurs when the cancer comes back after an initial treatment that was successful in destroying all detectable cancer at some point.
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