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

Abstract

Recent data on long-term outcomes and aggressiveness of medullary thyroid carcinoma (MTC) are lacking for patients with multiple endocrine neoplasia type 2 (MEN2). 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). 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. None (observational study). Long-term survival and outcomes in three risk groups. 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). 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.