Prognostic Impact of Serum Calcitonin and Carcinoembryonic Antigen Doubling-Times in Patients with Medullary Thyroid Carcinoma

Abstract

CONTEXT: After unsuccessful surgery, medullary thyroid carcinoma (MTC) may be fatal or remain stable for decades, and precise survival predictors are needed. OBJECTIVE: This study assesses the prognostic value of calcitonin and carcinoembryonic antigen (CEA) doubling-times (DT). DESIGN: This is a retrospective study on 65 MTC patients from 2.9-29.5 yr after surgery. SETTING: Data registered in the database of the French Neuroendocrine Tumor Group were analyzed anonymously. PATIENTS: All patients had abnormal calcitonin levels after total thyroidectomy and bilateral lymph node dissection. INTERVENTION: Calcitonin and CEA serum levels were measured during routine disease follow-up. MAIN OUTCOME MEASURE: To assess DT as prognostic factors, a patient population was extracted from the database. RESULTS: When calcitonin DT was less than 6 months, 5- and 10-yr survivals were three of 12 (25%) and one of 12 (8%), respectively; when between 6 months and 2 yr, 5- and 10-yr survivals were 11 of 12 (92%) and three of eight (37%), whereas all 41 patients with calcitonin DT greater than 2 yr were alive at the end of the study. Tumor-Node-Metastasis (TNM) stage, European Organization for Research and Treatment of Cancer (EORTC) score, and calcitonin DT were significant predictors of survival by univariate analysis, but only calcitonin DT remained an independent predictor of survival by multivariate analysis (P = 0.002) with a proportion of variance explained (PVE) of 37.4%. Calcitonin DT was a better predictor than CEA (PVE 63.3% and 47.0%, respectively). Calcitonin DT calculated using only the first four measurements was also an independent predictor of survival (P < 0.000001; PVE 40.4%). CONCLUSION: Calcitonin DT may be superior to initial clinical staging and among the most powerful prognostic indicators in MTC.