Pattern of Spread to the Lateral Neck in Metastatic Well-Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis

Background: There remains controversy surrounding the extent of lateral neck dissection required in patients with papillary thyroid cancer (PTC) and suspicious or confirmed metastatic lateral neck lymphadenopathy. The evidence for this clinical dilemma has never been reviewed systematically nor has there been an attempt to meta-analyze the data by lymph node levels to better characterize the pattern of spread. Methods: This meta-analysis used MEDLINE and EMBASE including all cohort studies reporting the pattern of lateral neck disease in patients who underwent a neck dissection for clinically, radiographically, or cytologically suspicious or confirmed metastatic lymphadenopathy for PTC. Our main outcome was the number of patients with positive involvement at a given level as a percentage of the cohort of patients with positive lateral neck disease, each level being measured separately. Results: Eighteen studies with a total of 1145 patients and 1298 neck dissections were included in our meta-analysis. Levels IIa and IIb had disease in 53.1% [95% confidence interval (CI) 46.6-59.5%] and 15.5% [CI 8.227.2%], respectively. Studies that did not distinguish between level IIa and IIb or in which both were collapsed into one category showed a total level II involvement of 53.4% [CI 49.7-57.1%]. Level III and level IV were involved in 70.5% [CI 67.0-73.9%] and 66.3% [CI 61.4-70.9%] of specimens. Studies that did not distinguish between level Va and Vb or in which both were collapsed into one category showed a total level V involvement of 25.3% [CI 20.0-31.5%]. Levels Va and Vb had positivity in 7.9% [CI 2.8-20.0%] and 21.5% [CI 7.7-47.6%], respectively, but had only three studies that could be meta-analyzed. Conclusions: This systematic review of the literature and meta-analysis of the pattern of spread indicates significant rates of lymph node metastasis to all lateral neck levels in patients with PTC with regional involvement. This evidence leads us to recommend a comprehensive selective neck dissection of levels IIa, IIb, III, IV, and Vb in patients with lateral neck disease from PTC. The evidence for level Va is lacking, as most studies did not distinguish between levels Va and Vb, and the border between the two levels was inconsistent. Future studies will need to address these sublevels separately.