Postoperative risk stratification using calcitonin doubling rate in medullary thyroid carcinoma with biochemical persistent disease

Abstract

Background: Biochemical persistent disease after surgery for medullary thyroid carcinoma is associated with an increased risk of recurrence; however, prognosis within this subgroup is heterogeneous. This study evaluated whether dynamic calcitonin-based growth kinetics, in addition to clinicopathologic factors, could stratify recurrence risk among patients with biochemical persistent disease.

Methods: This retrospective study included 265 patients who underwent surgery for medullary thyroid carcinoma at Kuma Hospital between 1997 and 2022. All patients underwent germline RET mutation analysis. A total of 65 patients with biochemical persistent disease who had sufficient postoperative calcitonin measurements for calculation of calcitonin doubling rate within 2 years after surgery were analyzed. Relapse-free survival was assessed using Kaplan-Meier analysis and Cox proportional analyses. Prognostic impact of calcitonin doubling rate and other factors on recurrence was analyzed using Cox regression analysis.

Results: During follow-up, 15 (23.1%) patients with biochemical persistent disease experienced recurrence. Receiver operating characteristic curve analysis identified an optimal calcitonin doubling rate cutoff of 0.3/y for recurrence prediction. Patients with calcitonin doubling rate ≥0.3/y had significantly worse relapse-free survival than patients with calcitonin doubling rate <0.3/y (log-rank P < .01), with 10-year relapse-free survival rates of 45.3% vs 89.2%. Multivariate analysis confirmed calcitonin doubling rate ≥0.3/y (hazard ratio 8.24, 95% confidence interval 2.31-29.48), tumor size >4 cm, and pathologic extrathyroidal extension as independent predictors of recurrence. Calcitonin doubling rate was inversely associated with age and showed no significant association with other classic clinicopathologic prognostic factors.

Conclusion: Dynamic assessment of postoperative calcitonin kinetics enables meaningful stratification of recurrence risk among patients with medullary thyroid carcinoma and biochemical persistent disease. Incorporation of calcitonin-based growth kinetics may support more individualized postoperative surveillance strategies.