Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma

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- NodeMetastasis ( 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.