BRAFV600E Is Correlated with Recurrence of Papillary Thyroid Microcarcinoma: A Systematic Review, Multi-Institutional Primary Data Analysis, and Meta-Analysis

Background: Given the increasing incidence of papillary thyroid carcinoma despite stable disease-specific mortality rates, the potential for the disease to reoccur is a key outcome to predict. The BRAF(V600E) mutation has been associated with recurrent disease in larger tumors. However, its correlation in papillary thyroid microcarcinoma (PTMC) is not clear in individual series. Methods: The MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for studies including patients with PTMC undergoing initial surgical treatment. Studies with at least two years of follow-up, BRAF genotyping (the comparator), and recurrence as an outcome were included, as were unpublished primary data on 485 patients from two institutions. The metameter analyzed was odds ratio (OR) for recurrence between patients with BRAF(V600E) versus BRAF wild type (BRAFwt). Results: The initial search identified 431 references. After screening of the abstracts for inclusion, 44 manuscripts were reviewed in full by two independent reviewers. Four published studies and primary data from two institutional cohorts were included in the final analysis. A meta-analysis of 2247 PTMC patients revealed that patients with a BRAF(V600E) mutation had a higher likelihood for recurrence (odds ratio 2.09 [confidence interval 1.31-3.33], p=0.002). Conclusions: This meta-analysis shows that BRAF mutational status correlates with recurrence of PTMCs, highlighting the potential utility of genotyping in preoperative and postoperative planning. BRAF mutation may be helpful in risk-stratifying patients with PTMC for surgical management versus observation.