Utility of Serum Procalcitonin for Screening and Risk Stratification of Medullary Thyroid Cancer

Context: The clinical utility of procalcitonin has not been demonstrated across the whole spectrum of medullary thyroid cancer (MTC). Objective: This serum biomarker validation study aimed at defining the diagnostic accuracy of procalcitonin for screening and risk stratification of MTC and delineating biochemical thresholds predictive of lymph node involvement in the neck and mediastinum. Design and Setting: This was a retrospective analysis at a tertiary referral center. Patients: Included in this study were 457 consecutive patients with previously untreated MTC, 112 of whom had procalcitonin and calcitonin serum levels determined before the initial operation. Intervention: The intervention was compartment-oriented surgery. Main Outcome Measures: Main outcome measures included primary tumor diameter, extrathyroidal extension, lymph node metastases, distant metastases, and biochemical cure. Results: Receiver operating characteristics analyses revealed similar diagnostic accuracy for procalcitonin vs the current calcitonin standard, yielding comparable areas under the curve for primary tumors at thresholds of 10 (0.94 vs 0.93) and 40 (0.92 vs 0.84) mm; extrathyroidal extension (0.84 vs 0.83), lymph node metastasis (0.88 vs 0.86), and distant metastasis (0.93 vs 0.91). Lymph node metastases were present in the ipsilateral lateral neck with procalcitonin levels <= 1.0 ng/mL and the ipsilateral central neck with procalcitonin levels <= 0.25 ng/mL. Above a threshold of 1.0 ng/mL, lymph node metastases emerged in the contralateral central and lateral neck and above 5.0 ng/mL also in the upper mediastinum. When procalcitonin levels exceeded 1, 5, 10, and 50 ng/mL, biochemical cure rates declined to no more than 71%, 36%, 23%, and 10%, respectively. Conclusion: Serum procalcitonin, having comparable diagnostic accuracy, has great potential to replace serum calcitonin as a new standard of care in the management of MTC because it does not need to be kept cool on ice or frozen and is easier to manage at the community level.