Sectioning Protocol Determines Accuracy of Intraoperative Pathological Examination of Sentinel Lymph Node in Cervical Cancer: A Systematic Review and Meta-Analysis

Abstract

Background: Sentinel lymph node biopsy (SLNB) is an efficient approach for detecting lymphatic metastasis in oncological surgeries. However, its benefits have long been confined by the lack of a precise intraoperative pathological examination. We therefore aimed to determine the diagnostic performance and optimal protocol of frozen section examination (FSE) in SLNB for cervical cancer. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure were searched from inception to April 30, 2019, for studies concerning SLNB combined with FSE in cervical cancer. Sensitivity of FSE in detecting SLN metastasis was the primary diagnostic indicator to be evaluated. Definitive pathological examination was the reference standard. Findings: The pooled sensitivity of FSE among 31 eligible studies (1887 patients) was 0·77 (95% credible interval [CI] 0·66-0·85) with high heterogeneity (Q=99·09, I2=69·73%). Two representative FSE protocols were identified from 26 studies, described as equatorial (E-protocol, SLN was bisected and sections were taken from the maximum surface) and latitudinal (Lprotocol, SLN was cut at intervals and sections were taken from each cutting surface). Meta-regression analysis showed that FSE protocol was the only source of heterogeneity (p 2 mm) were missed in 4 and 20 patients; small-volume metastases (≤2 mm) were detected in 13 and 2 patients, respectively, under L- and E-protocol. The pooled sensitivity of FSE using L-protocol would reach 0·97 (95% CI 0·89-0·99) if only marcometastases were considered. These findings were robust to sensitivity analyses. Interpretation: The sectioning protocol determines the accuracy of FSE in detecting SLN metastases. With L-protocol, FSE can provide precise intraoperative pathology for SLNB, which enables immediate decision-making for individualized managements. Funding Statement: Health and Medical Cooperation Innovation Special Program of Guangzhou Municipal Science and Technology. (Number: 158100075). Declaration of Interests: HT and J-HL report being investigators of an ongoing multicenter trial regarding SLNB in cervical cancer (CSEM 010, NCT02642471) funded by a government project (Health and Medical Cooperation Innovation Special Program of Guangzhou Municipal Science and Technology, Number: 158100075). J-HL receives lecture fees from AstraZeneca and Roche, outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: This study was registered with PROSPERO (CRD42019130044).