High-Sensitivity Calcitonin Testing Establishes New Cutoffs for Nodal Metastasis in Medullary Thyroid Cancer
Key Clinical Takeaways
- Design/Population: This multicenter retrospective cohort study evaluated 509 patients with medullary thyroid cancer who underwent preoperative basal calcitonin testing using modern electrochemiluminescence or chemiluminescence assays between 2011 and 2024. Patients were randomly assigned in a 2:1 ratio to training and validation cohorts to determine and confirm new calcitonin thresholds associated with varying extents of lymph node metastases.
- Key Outcomes: Updated calcitonin thresholds were identified for predicting central, ipsilateral lateral, contralateral or bilateral lateral, and upper mediastinal lymph node metastases, with levels ranging from approximately 242 pg/mL to nearly 2800 pg/mL. These new thresholds outperformed those recommended by the American Thyroid Association guidelines in predicting nodal involvement and distinguishing structural recurrence–free survival (RFS) in both cohorts.
- Clinical Relevance: Modern high-sensitivity calcitonin assays significantly change the biomarker thresholds historically used to estimate metastatic burden in medullary thyroid cancer. These updated cutoffs may improve preoperative risk stratification and guide selective neck dissection strategies in future prospective studies.
Results from a large multicenter cohort study demonstrate that contemporary high-sensitivity calcitonin assays significantly revise established serum calcitonin thresholds for predicting lymph node metastases in medullary thyroid cancer.
“Calcitonin is the most sensitive and specific biomarker for medullary thyroid cancer…[and] basal serum calcitonin levels are strongly associated with the burden of lymph node metastases… [which] can help guide the extent of neck dissection,” stated Yuxin Du, MD, Fudan University Shanghai Cancer Center, Shanghai, China, and coauthors. “However, the predictive thresholds for varying degrees of [lymph node metastases] are based on laboratory testing methods no longer in use.”
In this study, researchers collected data from 509 patients who underwent preoperative basal serum calcitonin testing using modern electrochemiluminescence or chemiluminescence assays at 13 hospitals between 2011 and 2024. Patients were randomized 2:1 to training and validation cohorts.
Using the training cohort, investigators identified preoperative basal calcitonin thresholds corresponding to different extents of lymph node metastases, including central, ipsilateral lateral, bilateral or contralateral lateral, and upper mediastinal involvement. These proposed thresholds were then evaluated in both cohorts for their ability to predict lymph node metastases and to distinguish structural recurrence-free survival (RFS).
At a median follow-up of 52 months, preoperative calcitonin levels demonstrated a positive correlation with increasing metastatic burden (η² = 0.28). Using the training cohort, optimal basal calcitonin thresholds were identified as 241.9 pg/mL for central lymph node metastases, 693.9 pg/mL for ipsilateral lateral lymph node metastases, 2,387.5 pg/mL for bilateral and/or contralateral lateral lymph node metastases, and 2,787.1 pg/mL for upper mediastinal lymph node metastases. When tested in both training and validation cohorts, these thresholds outperformed recommended guidelines for predicting lymph node metastases and for discriminating structural RFS.
“In this cohort study, updated threshold values of preoperative serum calcitonin predicted different extents of [lymph node metastases], which may provide optimal cutoffs for future prospective studies on biomarker-guided selective neck dissection in patients with [medullary thyroid cancer],” concluded Dr Du et al.
Source:
Du Y, Shen C, Song K, et al. Updated thresholds of basal calcitonin level and extent of lymph node metastasis in initially treated medullary thyroid cancer. JAMA Otolaryngol Head Neck Surg. Published online: June 26, 2025. doi:10.1001/jamaoto.2025.0542
