Impact of Minimal Extrathyroid Extension in Differentiated Thyroid Cancer: Systematic Review and Meta-Analysis

Background: Minimal extrathyroid extension (mETE) in patients with differentiated thyroid cancer (DTC) was defined as an intermediate risk feature in the 2015 American Thyroid Association guidelines. However, controversy persists as several studies suggested mETE has little effect on disease outcome. Objective: To assess the impact of mETE on DTC patients' outcome. Methods: Meta-analysis of controlled trials comparing patients with DTC with and without mETE. Data Extraction and Synthesis: Thirteen retrospective studies including 23,816 patients were included, with a median follow-up of 86 months. mETE in patients without lymph node involvement (N0 disease) was associated with increased risk of recurrence [seven studies: odds ratio (OR), 1.73; 95% confidence interval (CI), 1.03 to 2.92]. The absolute risk of recurrence was 2.2% in patients without extension and 3.5% in patients with mETE (P = 0.04). In studies including patients with and without lymph node involvement (N1/N0 disease), mETE resulted in a significantly higher risk of recurrence (eight studies: OR, 1.82; 95% CI, 1.14 to 2.91). The absolute risk of recurrence was 6.2% in patients without extension and 7% in patients with mETE (P = 0.01). In patients with micropapillary carcinoma (<1 cm), the impact of mETE was nonsignificant (OR, 2.40; 95% CI, 0.95 to 6.03). mETE had no impact on disease-related mortality (eight studies: OR, 0.5; 95% CI, 0.11 to 2.21). Conclusion: mETE increases risk of recurrence in patients with DTC; however, the absolute increase in risk is small, and in patients with N0 disease the risk is within the low-risk of recurrence category at 3.5%. mETE has no impact on disease-related mortality and should not change tumor stage.