Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d'Etude des Tumeurs Endocrines.

Background: In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent.

Objectives: To identify and characterize prognostic factors associated with disease-free survival (DFS) in children from HMTC families.

Design: We conducted a retrospective analysis of a multi-center cohort of 170 patients below age 21 at surgery. Demographic, clinical, genetic, biological data [basal and pentagastrine-stimulated calcitonin (CT and CT/Pg, respectively)], and tumor node metastasis (TNM) status were collected. DFS was assessed based on basal CT levels. Kaplan-Meier curves, Cox regression, and logistic regression models were used to determine factors associated with DFS and TNM staging.

Results: No patients with a preoperative basal CT <31 ng/ml had persistent or recurrent disease. Medullary thyroid carcinoma defined by a diameter ≥10 mm [hazard ratio (HR): 6.0; 95% confidence interval (95% CI): 1.8-19.8] and N1 status (HR: 20.8; 95% CI: 3.9-109.8) were independently associated with DFS. Class D genotype [odds ratio (OR): 48.5, 95% CI: 10.6-225.1], preoperative basal CT >30 ng/liter (OR: 43.4, 95% CI: 5.2-359.8), and age >10 (OR: 5.5, 95% CI: 1.4-21.8) were associated with medullary thyroid carcinoma ≥10 mm. No patient with a preoperative basal CT <31 ng/ml had a N1 status. Class D genotype (OR: 48.6, 95% CI: 8.6-274.1), and age >10 (OR: 4.6, 95% CI: 1.1-19.0) were associated with N1 status.

Conclusion: In HMTC patients, DFS is best predicted by TNM staging and preoperative basal CT level below 30 pg/ml. Basal CT, class D genotype, and age constitute key determinants to decide preoperatively timely surgery.