BRAF Mutation and Tumor Growth Kinetics during Active Surveillance of Papillary Thyroid Microcarcinoma: A Single-Center Retrospective Study

Background: We investigated tumor volume doubling time (TVDT) during active surveillance of papillary thyroid microcarcinoma (PTMC) and reviewed clinical factors including BRAF mutation associated with tumor progression. Methods: Patients with PTMC who deferred surgery for more than 1 year after diagnosis between 2014 and 2021 and were followed until 2023 were enrolled. Inclusion criteria were papillary thyroid carcinoma confirmed by fine needle aspiration cytology (Bethesda categories V-VI), maximal tumor diameter ≤1 cm, and available BRAF mutation testing. Results: A total of 85 patients were included. The median age was 49 years, and 63 patients (74%) were female. The positivity rate for BRAF mutation was 51% in the study cohort, and 16 patients (19%) showed rapid-growing disease, defined by a TVDT of less than 5 years. The median follow-up duration was 4.4 years, and 23 patients (27%) underwent surgery after a median of 3.2 years. When TVDT groups were analyzed using logistic regression, sonographic features with microcalcification were associated with tumor growth in binary regression (odds ratio for the group combining slowly and rapid-growing disease was 4.34; 95% confidence interval [CI], 1.41 to 13.35; P=0.010), and BRAF mutation was associated with rapid-growing disease in multinomial regression (odds ratio for rapid-growing disease was 4.48; 95% CI, 1.08 to 18.51; P=0.038). Conclusion: BRAF mutation is presumed to be associated with tumor progression and may predict growth of PTMC. Genetic testing including BRAF testing may help distinguishing rapid-growing thyroid cancer.