Long-Term Survivorship in Multiple Endocrine Neoplasia Type 2B Diagnosed Before and in the New Millennium

Context: Recent long-term outcomes and survival data are lacking for patients with multiple endocrine neoplasia type 2B (MEN2B). Objectives: To analyze long-term MEN2B outcomes and define prognostic factors. Design, Setting, and Participants: Retrospective comparative study of 75 patients with MEN2B from two German tertiary referral centers. Patients diagnosed and treated before and after 2000 were compared for demographic, biochemical, surgical, and outcome parameters. Intervention: Surgery. Main Outcome measure: Long-term survival. Results: We identified seven familial and 68 de novo cases of MEN2B; 61 exhibited the RET M918T genotype (2 others exhibited A883F and E768D/L790T mutations). Surgery was performed at a mean age of 16.46 +/- 1.2 years. The tumor stages at diagnosis for 71 patients were stage I, 15%; stage II, 6%; stage III, 35%; and stage IV, 44%. The mean follow-up was 9.6 +/- 9.0 years. The outcomes were 15 (20%) cured, 9 (12%) with minimal residual disease, 19 (25%) with metastatic disease, and 10 (13%) unknown. Medullary thyroid cancer (MTC) caused 22 deaths (29%) 7.3 +/- 6.2 years after diagnosis (mean age, 22.9 +/- 10.7 years). The overall survival rates at 5, 10, and 20 years were 85%, 74%, and 58%, respectively. After 2000 (vs before 2000), significantly more patients had stage I and II (32% vs 11%) and more were cured (43% vs 20%), with a higher survival trend (P = 0.058). The only prognostic factor was tumor stage at diagnosis. Conclusions: Patients with MEN2B developed MTC at an early age with wide ranging aggressiveness, but the outcome was generally better after 2000 than before 2000.