Clinicopathologic predictors of central lymph node metastases in clinical node-negative papillary thyroid microcarcinoma: a systematic review and meta-analysis

Abstract

Background: The presence of central lymph node metastases (CLNM) has been suggested as a risk factor for poorer prognosis and recurrence in papillary thyroid microcarcinoma (PTMC). However, the clinicopathologic factors for CLNM in clinical node-negative (CN0) PTMC were not well defined. This study aimed to perform a systematic review and meta-analysis to investigate the significant clinicopathologic predictors of CLNM in CN0 PTMC. Methods: A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science. Case-control studies on the association of clinicopathologic risk factors with CLNM in CN0 PTMC were included. Results: Thirteen eligible studies involving 6068 patients with CN0 PTMC were included. From the pooled analyses, male (odds ratio [OR]: 2.07, 95% CI: 1.49–2.87, P < 0.001), multifocality (OR: 1.88, 95% CI: 1.54–2.29, P < 0.001), tumor size > 5 mm (OR: 1.84, 95% CI: 1.55–2.18, P < 0.001), and extrathyroidal extension (OR: 1.96, 95% CI: 1.30–2.95, P = 0.001) are significantly associated with increased risk of CLNM in CN0 PTMC. A sample size with a cutoff point of 200 was identified as the source of heterogeneity for sex according to meta-regression (t = 3.18, P = 0.033). Then, the subgroup analysis of male was performed, which illustrated that male increased the risk of CLNM in the small sample group (SG) and the large sample group (LG) by 6.11-folds and 2.01-folds, respectively (SG: OR, 6.11, 95% CI, 3.16–11.81, P < 0.001; LG: OR, 2.01, 95% CI, 1.65–2.46, P < 0.001). Conclusions: Male, multifocality, tumor size > 5 mm, and extrathyroidal extension may be reliable clinical predictors of CLNM in CN0 PTMC. Moreover, prophylactic central lymph node dissection should be considered in surgical decision-making for CN0 PTMC patients, who are male, multifocal, with tumor size > 5 mm, and with extrathyroidal extension. Trial registration: CRD42021242211 (PROSPERO)