Prognostic impact of extra-nodal extension in thyroid cancer: A meta-analysis

Lymph node involvement is common in thyroid cancer, but the system of staging does not consider the histological features of lymph node metastases. We conducted a meta-analysis to investigate the prognostic role of extranodal extension (ENE) in thyroid cancer patients. We ran PubMed and SCOPUS searches without language restrictions. Prospective studies reporting data on overall mortality, cancer-specific mortality, or disease recurrence including thyroid cancer patients, in which cases with ENE (ENE+) were compared with those with only intranodal disease (ENE-) were eligible. Data were summarized using risk ratios (RR) for number of deaths/recurrences, and hazard ratios (HR) for time-dependent risks related to ENE+ status, adjusted for potential confounders. Of 414 hits, 23 studies were eligible and included. Compared to ENE-, patients who were ENE+ had significantly higher rates of all-cause mortality (studies = 8; RR = 3.25; 95%CI: 1.35-2.64, I(2) = 83%) and recurrence (studies = 17; RR = 2.64, 95%CI: 1.93-3.60, I(2) = 73%). Using HRs adjusted for potential confounders, ENE+ status carried a significantly higher risk of all-cause and cancer-specific mortality and disease recurrence. It becomes mandatory to consider ENE in the histopathological examination of surgical samples in thyroid cancer patients, and this factor should be included in future oncological staging systems