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

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.