Fernández González Sergi

Prognostic significance of molecular classification in high-risk endometrial cancer patients undergoing sentinel lymph node mapping

The adoption of selective sentinel lymph node biopsy (SLNB) as a viable alternative to lymphadenectomy, along with the redefinition of nodal risk groups based on molecular classification, has significantly changed the management of early-stage, high-risk preoperative endometrial cancer. A retrospective, multicenter study was conducted under the auspices of the Spanish Gynecologic Oncology Group to evaluate recurrence rates and oncologic outcomes in patients stratified by molecular risk. Three groups were compared: SLNB alone (G1), SLNB combined with pelvic and/or para-aortic lymphadenectomy (G2), and pelvic and/or para-aortic lymphadenectomy without SLNB (G3). The primary endpoint was recurrence rate; secondary endpoints included disease-free survival (DFS), overall survival (OS), recurrence patterns. A total of 221 patients from 14 centers were included, with a median follow-up of 24.4 months (IQR 17-42). Forty-four patients (19.9 %) experienced recurrence. Relapse rates were 15.4 % in G1, 15.8 % in G2, and 22.2 % in G3 (p = 0.479). DFS rates were 84.6 % in G1, 84.1 % in G2, and 77.8 % in G3 (p = 0.56). OS rates were 94.2 %, 90.9 %, and 92.6 %, respectively (p = 0.651). Among the 44 patients with documented recurrence, seven had nodal recurrences, with only two occurring in the group managed with SLNB alone. In this study, patients with early-stage, high-risk preoperative endometrial cancer-classified by molecular subgroups-showed no significant differences in relapse rates, disease-free survival, or overall survival across the three management strategies. Further prospective studies with longer follow-up are warranted to validate these preliminary findings.

SENECA study: staging endometrial cancer based on molecular classification

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-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. The SENECA study retrospectively reviewed data from 2139 women with stage I-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. 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-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). 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.