Endocrine Abstracts

Introduction: Calcitonin (CT) is the most specific marker for medullary thyroid carcinoma (MTC), thus, even low detectable values can conceal persistent disease. Current guidelines suggest performing an early CT evaluation three months after surgery. However, this timing may be too premature to evaluate the CT nadir, since different isoforms or aggregates from tumour deposits may persist in the bloodstream and require additional time to be cleared. The present study aimed to explore the prognostic role of pre-operative and early CT levels, in MTC patients without distant metastases at diagnosis.

Methods: A retrospective cohort of patients suffering from medullary thyroid carcinoma without distant metastases at diagnosis was considered (n=55). The final disease status, i.e. complete response (undetectable CT levels and negative radiological assessments) or persistent disease (detectable CT levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early CT levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status.

Results: Persistent disease patients (n=27) showed higher pre- and early CT values (P=0.028 and P<0.001, respectively), compared to complete response sub-cohort (n=28). After a median follow-up of 39.2 months [16.3-83.7], six patients died, while 12 patients (21%) developed distant metastases. A pre-surgical CT value of 284 pg/ml showed a sensitivity of 69.2% and a specificity of 68.0 % in predicting the final outcome (AUC= 0.679, CI95:0.525-0.833, P=0.028). In a similar ROC model, the lowest detectable CT value at six months follow-up (i.e. 0.7 pg/ml) of the present cohort was able to predict the final outcome with a sensitivity and a specificity of 95.8 % and 80.0%, respectively (AUC= 0.958, CI95: 0.900-1.0, P<0.001). In fact, only five patients (9.1% of the population) with a final complete response status showed early detectable CT values. The cox-regression model shows that early detectable CT levels increase up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (O r=18.53, CI95%: 2.25-152.8, P=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early CT level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, P<0.001).

Conclusions: CT levels six months after surgery are an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastases at diagnosis.