The Impact of the BRAF V600E Mutation on Recurrence and Survival in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis

The prognostic value of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) remains uncertain, partly because persistent disease and true recurrence have often been combined and overlapping cohorts and effect measures have been handled inconsistently. This systematic review and meta-analysis evaluated recurrence and survival outcomes while distinguishing strict recurrence—new disease after a documented disease-free state—from broader persistent/recurrent endpoints. A systematic search through 1 June 2026 identified 34 eligible publications, of which 25 contributed to quantitative analyses. The exploratory strict-recurrence hazard ratio (HR) analysis included three studies (674 patients) and was highly imprecise (HR 1.84; 95% CI, 0.33–10.28; I2 = 53.6%). Nine cohorts (2393 patients; 152 recurrences) contributed to the strict-recurrence risk ratio (RR) analysis, showing a higher observed recurrence risk with BRAF V600E (RR 1.88; 95% CI, 1.33–2.66; I2 = 0%). Restriction to structurally confirmed recurrence yielded a less precise association (RR 1.56; 95% CI, 0.95–2.57). Broad-outcome associations were weaker and attenuated after exclusion of persistence-heavy endpoints (RR 1.03; 95% CI, 0.69–1.54). Disease-specific mortality evidence was sparse and exploratory. Thirty-two of 36 model-specific QUIPS assessments met our operational high-concern category. BRAF V600E is therefore associated with a higher observed crude risk of recurrence after documented remission, but adjusted evidence is insufficient to establish independent prognostic value. Clinically, isolated BRAF status should be interpreted as contextual molecular information rather than a management directive: the available evidence does not show sufficient incremental value beyond postoperative pathology and response-to-therapy assessment to alter surgery, radioiodine treatment, or surveillance on its own.