Objective Management of endometrial cancer is advancing, with accurate staging crucial
for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement
rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage
(International Federation of Gynecology and Obstetrics 2009 I & acirc;"II) endometrial
cancer, considering molecular subtypes and new European Society of Gynaecological
Oncology (ESGO) risk classification. Methods The SENECA study retrospectively reviewed
data from 2139 & acirc;parts per thousand women with stage I & acirc;"II
endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with
SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular
analysis was performed on pre-operative biopsies or hysterectomy specimens. Results
Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53
abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%)
mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion
was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion
observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic
acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected
sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume
metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while
66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed
between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50%
and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004);
(p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31),
p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients,
6.62% for intermediate-risk patients, 21.63% for high & acirc;"intermediate
risk patients, and 22.51% for high-risk patients; p<0.001). Conclusions Our study
reveals significant differences in SLN involvement among patients with early-stage
endometrial cancer based on molecular subtypes. This underscores the importance of
considering molecular characteristics for accurate staging and optimal management
decisions.
