American Journal of Obstetrics and Gynecology
Systematic ReviewsSentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics
Introduction
Endometrial cancer (EC) is the most common gynecologic cancer in developed countries.1 The incidence of both low- and high-grade EC continues to increase secondary to the rising rates in obesity and life expectancy.1, 2, 3 Because high-grade EC is less likely to be associated with estrogen-related risk factors and obesity, other unknown factors may also play a role in its rising incidence.3,4
The standard management of early-stage, high-grade EC includes hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection to determine the stage of disease and the need for adjuvant treatment.5,6 However, a complete pelvic lymphadenectomy (PLND) and para-aortic lymphadenectomy (PALND) are associated with substantial morbidity (nerve or vessel injury, blood loss, lymphocyst formation, and lymphedema) and adverse impacts on the quality of life.7, 8, 9
A sentinel lymph node biopsy (SLNB) based on the Memorial Sloan Kettering sentinel lymph node (SLN) algorithm10 has gained acceptance as an alternative to a full lymphadenectomy in low-grade EC (grade 1 or 2 endometrioid).6,11 The SLN algorithm includes peritoneal and serosal evaluation, retroperitoneal excision of the successfully mapped SLN in each hemipelvis, removal of any suspicious nodes, and most importantly, full side-specific PLND and PALND for failed mapping.10 SLNs are then processed using ultrastaging, defined as additional serial sectioning and review of multiple hematoxylin and eosin (H&E) stained slides with cytokeratin immunohistochemistry (IHC) staining when H&E sections are negative.6,11 The exact protocols vary across different centers.12,13
The role of SLNBs in high-grade EC (grade 3 endometrioid, serous, clear cell, carcinosarcoma, dedifferentiated, and mixed histology) is less clear. The majority of studies on SLNBs in EC included patients with low-grade EC who are known to be at lower risk for lymph node involvement.7 Several studies have examined SLNBs in patients with a mix of high-risk features; however, only a subset specifically included patients with high-grade histology, including 13% in the Sentinel Node and Endometrial Cancer study,14 28% in the FIRES study,15 46% in the Pelvic Sentinel Lymph Node Detection in High-Risk Endometrial Cancer (SHREC) trial,16 and 80% in a study by Soliman et al.17 The recently published Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging (SENTOR) study had the largest cohort of patients with high-grade histology to date, used a contemporary tracer, and showed that SLNBs had acceptable diagnostic accuracy in this group of patients.18
Application of an SLNB in patients with high-grade EC may be associated with different performance characteristics and requires more evidence of accuracy before becoming the standard of care. We therefore performed a systematic review and meta-analysis to evaluate the performance characteristics of SLNBs using indocyanine green (ICG) among patients with EC with high-grade histologic subtypes who underwent a complete PLND (with or without PALND) as a reference standard.
Section snippets
Eligibility criteria
The protocol for this study was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) under identifying number CRD42020160280, conducted according to the Cochrane Handbook,19 and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis20 and the Meta-Analysis of Observational Studies in Epidemiology21 guidelines. We included prospective cohort studies that (1) evaluated SLNBs with cervical injection of ICG; (2)
Study selection
We identified 8620 records in the database searches from January 1, 2000, to January 26, 2021 (Figure 1). Seven additional records were identified through manual searching and citation tracking. Following the exclusion of duplicates, 5897 articles were left for evaluation. After title and abstract screening, 262 articles were selected for full-text screening.
Of the 262 full-text articles, 246 were excluded for reasons outlined in Figure 1 and Appendix 2 (Supplemental Table 2). There ultimately
Comment
In this comprehensive systematic review of 16 studies and 429 patients with high-grade EC eligible for meta-analysis we found (1) high pooled detection rates of 91% per patient (95% CI, 85%–95%; I2=59%) and 64% bilaterally (95% CI, 53%–73%; I2=69%); (2) high pooled sensitivity of 92% per patient (95% CI, 84%–96%; I2=0%) and 90% per hemipelvis (95% CI, 83%–94%; I2=0%); (3) high pooled NPV of 97% per patient (95% CI, 95%–99%; I2=0%) and 98% per hemipelvis (95% CI, 96%–99%; I2=8%).
Our findings are
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The authors report no conflict of interest.
This study received no financial support.