PT - JOURNAL ARTICLE AU - Chacon, Enrique AU - Boria, Felix AU - Lyer, R Rajagopalan AU - Fanfani, Francesco AU - Malzoni, Mario AU - Bretová, Petra AU - Luzarraga Aznar, Ana AU - Fruscio, Robert AU - Jedryka, Marcin A AU - Tóth, Richard AU - Perrone, Anna Myriam AU - Kakkos, Athanasios AU - Cristóbal Quevedo, Ignacio AU - Congedo, Luigi AU - Zanagnolo, Vanna AU - Fernandez-Gonzalez, Sergi AU - Ferro, Beatriz AU - Narducci, Fabrice AU - Hovhannisyan, Tatevik AU - Aksahin, Elif AU - Cardenas, Laura AU - Oliver, M Reyes AU - Nozaleda, Gonzalo AU - Arnaez, Marta AU - Misiek, Marcin AU - Ferrero, Annamaria AU - Pain, Flore Anne AU - Zarragoitia, Janire AU - Diaz, Cristina AU - Ceppi, Lorenzo AU - Mehdiyev, Shamsi AU - Roldán-Rivas, Fernando AU - Guijarro-Campillo, Alberto Rafael AU - Amengual, Joana AU - Manzour, Nabil AU - Sanchez Lorenzo, Luisa AU - Núñez-Córdoba, Jorge M AU - Gonzalez Martin, Antonio AU - Minguez, Jose Angel AU - Chiva, Luis ED - , TI - SENECA study: staging endometrial cancer based on molecular classification AID - 10.1136/ijgc-2024-005711 DP - 2024 Sep 01 TA - International Journal of Gynecologic Cancer PG - 1313--1321 VI - 34 IP - 9 4099 - http://ijgc.bmj.com/content/34/9/1313.short 4100 - http://ijgc.bmj.com/content/34/9/1313.full SO - Int J Gynecol Cancer2024 Sep 01; 34 AB - 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–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 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.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–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.All data relevant to the study are included in the article or uploaded as supplementary information.