Long-Term Follow-Up in Medullary Thyroid Carcinoma Patients

Abstract

After surgery, patients with MTC (medullary thyroid carcinoma) should be assessed for the presence of residual disease, the localization of metastases, and the identification of progressive disease. Postoperative staging is used to separate low-risk patients from high-risk patients with MTC. In addition to the TNM system, further histological staging with Ki67, mitotic count, tumor necrosis, and molecular analysis of somatic RET mutations is helpful for the stratification of patients in different prognostic categories. The number of lymph node metastases and involved compartments as well as postoperative Ctn (calcitonin) and CEA (carcinoembryonic antigen) levels should also be documented. Postoperative nonmeasurable Ctn levels are associated with a favorable outcome. In patients with basal serum Ctn levels less than 150 pg/ml following thyroidectomy, persistent or recurrent disease is almost always confined to lymph nodes in the neck. If the postoperative serum Ctn level exceeds 150 pg/ml, patients should be evaluated by imaging procedures, including neck and chest CT (computed tomography), contrast-enhanced MRI, US of the liver, bone scintigraphy, MRI of the bone and positron emission tomography (PET)/CT. One can estimate the growth rate of MTC metastases from sequential imaging studies using response evaluation criteria in solid tumors (RECIST) that document increases in tumor size over time and by measuring serum levels of Ctn or CEA over multiple time points to determine the tumor marker doubling time. One of the main challenges remains finding effective adjuvant and palliative options for patients with metastatic disease. Patients with persistent or recurrent MTC localized to the neck and slightly elevated Ctn levels following thyroidectomy might be candidates for neck reoperations depending on the extent of the tumor. Once metastases appear, the clinician must decide which patients require therapy, balancing the frequently slow rate of tumor progression associated with a good quality of life and suggesting active surveillance against the limited efficacy and potential toxicities of local and systemic therapies. Considering that metastatic MTC is incurable, the management goals are to provide locoregional disease control, palliate symptoms such as diarrhea, palliate symptomatic metastases causing pain or bone fractures, and control metastases that threaten life through bronchial obstruction or spinal cord compression. This can be achieved by palliative surgery, EBRT (external beam radiation therapy) or systemic therapy using multikinase inhibitors (MKIs) targeting RET or selective RET inhibitors requiring genetic testing prior to the initiation of therapy.

Keywords: Calcitonin; Carcinoembryonic antigen; Medullary thyroid carcinoma; Multiple endocrine neoplasia; Somatic RET mutation; Tyrosine kinase inhibitors.