Sporadic medullary thyroid cancer: a systematic review and meta-analysis of clinico-pathological and mutational characteristics predicting recurrence

Introduction: Sporadic medullary thyroid cancer accounts for 75% of all medullary thyroid cancers and presents at a more advanced disease stage than its hereditary counterparts. Yet there is little evidence to support risk stratification of patients according to risk of recurrence. Methods: A systematic review and meta-analysis was performed investigating clinical and pathological factors that are associated with recurrent disease in patients with medullary thyroid cancer. Results: 10 studies totalling 458 patients were included in the meta-analyses. T3 and T4 disease (OR 9.33 (95% CI 2.5 - 34.82) p = 0.0009.), AJCC stage III and IV disease (OR 13.34 (95% CI 2.9 - 60.3) p = 0.0008) and the presence of nodal disease (OR 7.28 (95% CI 7.2-43.3) p = 0.03) were all associated with recurrent disease. RET mutations (OR 0.08 (95% CI -0.03-0.19) p = 0.17) and RET 918 T mutations (OR 1.77 (95% CI 0.804.0) P = 0.17) were not associated with disease recurrence. It was not possible to pool data with respect to extrathyroidal extension, extracapsular extension, peri-neural and lymphovascular invasion and RAS mutations. Conclusion: T3 and T4 disease, AJCC stage III and IV disease and the presence of nodal disease are associated with recurrent disease. The heterogeneous reporting of recurrence and the lack of individual patient data precludes larger scale meta-analyses. Future research in this area should involve collaboration to establish standardised definitions of disease recurrence.