Updated Thresholds of Basal Calcitonin Level and Extent of Lymph Node Metastasis in Initially Treated Medullary Thyroid Cancer

Abstract

Importance: Calcitonin is the most sensitive and specific biomarker for medullary thyroid cancer (MTC). Basal serum calcitonin levels are strongly associated with the burden of lymph node metastasis (LNM) and can help guide the extent of neck dissection. However, the predictive thresholds for varying degrees of LNM are based on laboratory testing methods no longer in use.

Objective: To update the optimal thresholds of basal serum calcitonin levels for predicting the extent of LNM.

Design, setting, and participants: This retrospective cohort study included initially treated patients with MTC who had their preoperative basal calcitonin levels tested using electrochemiluminescence or chemiluminescence from a Chinese multicenter cohort of 13 hospitals between 2011 and 2024. The patients were randomly divided into a training and a validation cohort in a 2:1 ratio. The data were analyzed between June 2024 and September 2024.

Exposures: Preoperative basal serum calcitonin using electrochemiluminescence or chemiluminescence.

Main outcomes and measures: The main outcome is Structural recurrence-free survival (SRFS) based on the group partitioned by the proposed thresholds predicting different LNMs.

Results: A total of 509 patients were included in the study with a median (interquartile range [IQR]) follow-up of 52 (27-84) months. The median (IQR) age at diagnosis was 50 (40-59) years, and 279 patients (54.8%) were female individuals. Patients were categorized into 4 groups based on the extent of LNM: no LNM, central LNM, lateral LNM, and upper mediastinal LNM. A positive correlation was found between preoperative calcitonin levels and the extent of LNM (η2 = 0.28). Using the training cohort, preoperative basal calcitonin thresholds associated with different extents of LNM were identified as follows: 241.9 pg/mL for central LNM, 693.9 pg/mL for ipsilateral lateral LNM, 2787.1 pg/mL for upper mediastinal LNM, and 2378.5 pg/mL for bilateral and/or contralateral lateral LNM. In both the training and validation cohorts, the proposed thresholds outperformed those recommended by the American Thyroid Association guidelines not only in the prediction of LNM, but also in the discrimination of SRFS.

Conclusions: In this cohort study, updated threshold values of preoperative serum calcitonin predicted different extents of LNM, which may provide optimal cutoffs for future prospective studies on biomarker-guided selective neck dissection in patients with MTC.