Long-Term Outcomes and Aggressiveness of Hereditary Medullary Thyroid Carcinoma: 40 Years of Experience at One Center.

Context: Recent data on long-term outcomes and aggressiveness of medullary thyroid carcinoma (MTC) are lacking for patients with multiple endocrine neoplasia type 2 (MEN2).

Objectives: To analyze the long-term outcomes in MEN2 and compare MTC aggressiveness in three defined RET mutation-risk categories: moderate risk (MOD), high risk (H), and highest risk (HST).

Design, Setting: Retrospective study of 263 operated patients with MEN2 from one German tertiary referral center from 1979 to 2017 comparing demographic, biochemical, genetic, and outcome parameters.

Intervention: None (observational study).

Main Outcome Measure: Long-term survival and outcomes in three risk groups.

Results: Surgery was performed at a mean age of 35.3 ± 18.8 (MOD, n = 122), 23.0 ± 15.7 years (H, n = 120), and 14.9 ± 9.3 (HST, n = 21) years (P < 0.05). The mean follow-up was 12.9 ± 9.8 years. Age and tumor stage at diagnosis differed among the three risk groups (P < 0.0001). Multivariate analysis of disease-specific survival (DSS) showed that increasing age [hazard ratio (HR), 1.06; 95% CI, 1.02 to 1.09], stage III/IV at diagnosis (HR, 7.39; 95% CI, 2.39 to 22.8), and HST group (HR, 14.4; 95% CI, 3.32 to 62.6) were significantly associated with worse DSS; the H group was not (P = 0.175). The DSS rates and outcomes were not different between the MOD and H groups (P = 0.179 and P = 0.893, respectively) but were significantly inferior in the HST group (P < 0.0008 and P < 0.0001, respectively).

Conclusion: MTC in patients with MEN2 showed a clearly different age of onset in the different risk groups. DSS and outcomes after MTC diagnosis were similar in the MOD and H groups, suggesting similar tumor behavior. The HST group had inferior outcomes and survival vs the MOD and or H groups.