Independent Prognostic Value of BRAF V600E for Recurrence in Papillary Thyroid Carcinoma: A Systematic Review and...

Background: The independent prognostic value of BRAF V600E in papillary thyroid carcinoma (PTC) remains uncertain. Current risk stratification schemes incorporate BRAF inconsistently, reflecting uncertainty about its independent association with recurrence. A systematic review and meta-analysis were conducted to evaluate the association between BRAF V600E and recurrence-related outcomes in PTC. Methods: PubMed and Embase were searched for observational cohort studies reporting recurrence, recurrence-free survival, or disease-free survival according to BRAF status and providing multivariate-adjusted hazard ratios (HRs). Primary analysis included studies in which multivariate models adjusted for tumor size or American Joint Committee on Cancer (AJCC) tumor (T) category, whereas sensitivity analysis included all eligible multivariate studies irrespective of tumor size adjustment. Random-effects models were used to pool HRs with 95% confidence intervals (CIs), and heterogeneity was quantified with I². Thirty-five cohort studies (n = 14,982 patients) met the inclusion criteria. Results: In the primary analysis of 27 studies adjusting for tumor size or T category, BRAF V600E was associated with a 58% higher risk of recurrence (pooled HR 1.58, 95% CI 1.25-1.99; I² = 56.2%). In the sensitivity analysis, results remained consistent (pooled HR 1.40, 95% CI 1.11-1.76; I² = 64.5%). The funnel plot and Egger's regression test did not indicate substantial publication bias. Conclusions: Overall, BRAF V600E was associated with a modest but statistically significant increase in recurrence risk in PTC after adjustment for tumor size or T category. However, given the heterogeneity of included studies and variability in multivariable adjustment, these findings should be interpreted as supporting BRAF V600E as a complementary rather than a standalone prognostic marker.