The prognostic significance and role of adjuvant therapy for low-volume nodal metastasis in apparent early stage endometrial cancer: an updated systematic review and meta-analysis.

Sentinel lymph node biopsy (SLNB) has improved detection of low-volume node metastasis (LVNM) in endometrial cancer (EC), but its prognostic significance and the need for adjuvant therapy (AT) remain unclear. A comprehensive search was performed until August 31, 2024 in multiple databases and sources. From 21 studies, 65,228 apparent early-stage EC patients were identified: 370 with macrometastases (MAC), 526 with micrometastases (MM), 2,138 with isolated tumor cells (ITCs), and 62,194 with negative nodes. Findings indicated: 1) The MM group had a lower risk of recurrence or progression (R/P) than the MAC group (risk ratio [RR]=0.49; 95% confidence interval [CI]=0.31-0.78; p=0.002), higher risk than the negative nodes group (RR=2.07; 95% CI=1.59-2.68; p<0.001), and similar risk to the ITC group (RR=0.67; 95% CI=0.44-1.02; p=0.060). 2) The MM group had higher 3-year progression-free survival (PFS) (RR=1.36; 95% CI=1.21-1.52; p<0.001) and overall survival (OS) (RR=1.22; 95% CI=1.09-1.37; p<0.001) than the MAC group, similar to the ITC and negative nodes groups. 3) The ITC group had a lower R/P risk and higher 3-year PFS/OS than the MAC group, similar to the negative nodes group. 4) AT reduced the R/P risk in the MM group (RR=0.41; 95% CI=0.22-0.76; p=0.005) and increased 3-year OS in the ITC group (RR=1.06; 95% CI=1.04-1.08; p<0.001). Early-stage EC with LVNM had better prognostic outcomes than MAC, and AT may improve outcomes of LVNM patients. More evidence from prospective randomized controlled trials is needed to confirm these findings due to the inherent biases of retrospective studies. Trial Registration PROSPERO Identifier: CRD42022364536.