Background: Given the good prognosis of low-risk papillary thyroid microcarcinomas (lrPTMCs) accurate risk stratification is valuable to optimize management: active surveillance vs. surgery. BRAFV600E testing was associated with increased recurrence risk, hence AS seems reasonable for mutation-negative lrPTMC. However, when considering AS, patient perception is highly important as adherence and emotional aspects are challenging. In this study, we aimed to model the contribution of BRAFV600E testing for the management of PTMCs when tailored to the patient perspective. Methods: We developed a Markovian model to predict the role of BRAFV600E in prioritizing between hemithyroidectomy (HT) and active surveillance (AS) for lrPTMCs. We used a simulated cohort of lrPTMCs, with probabilities of each strategy driven from previous literature. Outcomes were measured as quality-of-life years (QALYs). One- and two-way sensitivity analyses were conducted to ascertain model robustness. Results: We found that the optimal strategy (e.g., that would maximize QALYs) varies according to BRAFV600E status for patients without a preset predilection between AS to HT. Using one-way sensitivity analysis, we found that the two main variables that have the strongest impact on the decision are the utility of AS and the utility of a disease-free state after HT. Two-way sensitivity analysis demonstrated that BRAFV600E status can define the optimal strategy for patients in the middle zone of the utility range (e.g., patients without clear preference). Conclusions: Our model suggests that BRAFV600E status can facilitate decision-making regarding AS vs. HT for patients without preset predilection. Our model supports further real-life studies of BRAFV600E testing for PTMCs.

Objective: The aim of this study was to ascertain the relationship between Bethesda category and molecular mutation of thyroid nodules in patients undergoing thyroidectomy. Design: A retrospective cohort of patients who underwent thyroidectomy following needle biopsy and molecular profile testing was performed. Setting: Two tertiary care academic hospitals. Participants: Consecutive patients with a dominant thyroid nodule who underwent both USFNA and molecular profile testing followed by thyroidectomy were included in the study. Main Outcome and Measures: The main outcome was postoperative diagnosis of thyroid cancer and aggressivity of disease based on histopathological variants, nodal metastasis or extra-thyroidal extension. Associations between Bethesda category, molecular mutation and postoperative pathology was assessed using descriptive analysis and Chi-square testing. Results: 451 patients were included. 95.9% (93/97) of patients with a BRAFV600E mutation had a Bethesda category V or VI (P<0.001), and all had confirmed thyroid cancer on postoperative pathology. Those with H, K or N RAS or EIF1AX mutations, gene expression profiling (GEP) or copy number alterations showed an association with Bethesda categories III and IV (P≤0.01). Those with no identified molecular mutation had a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs 44.3%, P<0.01). Conclusion: BRAFV600E mutations were associated with thyroid cancer subtypes known to be more aggressive. These findings may help thyroid specialists better identify aggressive thyroid nodules associated with indeterminate Bethesda categories.