Risk-stratified follow-up of patients with medullary thyroid carcinoma

Abstract

Medullary thyroid carcinoma (MTC) is a differentiated neuroendocrine tumor, mostly slowly growing with a relative good prognosis, with an overall 10-year survival of 61–76% [1,2]. Surgery is the only curative therapy for MTC [3]. After surgery, patients with MTC should be assessed regarding the presence of residual disease, the localization of metastases and the identification of progressive disease. Postoperative staging is used to separate low-risk from high-risk patients with MTC [4]. The TNM system utilizes tumor size, extrathyroidal invasion, nodal metastasis and distant spread of cancer. The number of lymph node metastases and involved compartments as well as postoperative serum calcitonin (CTN) and carcinoembryonic antigen (CEA) levels should be documented in addition. The normalization of serum CTN levels postoperatively is associated with an excellent prognosis (10-year survival >95%). In patients with elevated basal serum CTN levels less than 150 pg/ml following thyroid ectomy, persistent or recurrent disease is almost always confined to lymph nodes in the neck. Unfortunately, many patients with MTC who have regional lymph node metastases also have systemic disease and are not cured biochemically despite aggressive surgery, including bilateral neck dissection [3,5]. In patients with higher CTN levels distant metastases are suspected, having a poor prognosis, with only 40% surviving 10 years [6]. If the postoperative serum CTN level exceeds 150 pg/ml patients should be evaluated by imaging procedures including neck and chest CT, contrast-enhanced MRI and ultrasound of the liver, bone scintigraphy, MRI of the bone and PET/CT. One can estimate the growth rate of MTC metastases from sequential imaging studies using response evaluation criteria in solid tumors (RECIST) [7] 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 [8,9]. The treatment goals differ depending on the postoperative tumor stage and the parameters of progressive disease [4]. A risk-stratified follow-up with stage-dependent diagnostic approach and therapy is necessary. One of the main challenges remains to find effective adjuvant and palliative options for patients with metastatic disease. Patients with persistent or recurrent 1