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Publications

Journal Article Epublish

PubMed: 42755952 DOI: 10.3389/fonc.2026.1810138

Oncologic safety of sentinel lymph node-based nodal de-escalation in apparent uterine-confined endometrial cancer: a multicenter international cohort study.

Front Oncol 16:1810138

Authors: Alessandro Buda, Ilaria Capasso, Jessica Mauro, Emanuele Perrone, Michael Mueller, Robert Fruscio, Valentina Bruno, Sara Imboden, Tommaso Grassi, Virginia Garcia-Pineda, Elisa Tripodi, Salih Taskin, Stefano Restaino, Diego Raimondo, Vito Andrea Capozzi, Andrea Papadia, Franziska Siegenthaler, Jvan Casarin, Giuseppe Cucinella, Enrico Vizza, Ignacio Zapardiel, Giuseppe Vizzielli, Cagatay Taskiran, Francesco Fanfani

Affiliations

  • Division of Gynecologic Oncology, Michele and Pietro Ferrero Hospital, Verduno, Italy.
  • Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Gynaecological Oncology, Inselspital University Hospital Berne Department of Gynaecology, Bern, Switzerland.
  • Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
  • Division of Gynecology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
  • Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Gynecologic Oncology Unit, La Paz University Hospital, Madrid, Spain.
  • Department of Obstetrics and Gynecology, School of Medicine, Ankara University, Ankara, Türkiye.
  • Santa Maria Misericordia Hospital, University of Udine, Udine, Italy.
  • Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  • Department of Obstetrics and Gynecology, University of Parma, Parma, Italy.
  • Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale, Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
  • Department of Obstetrics and Gynecology, 'Filippo Del Ponte' Hospital, University of Insubria, Varese, Italy.
  • Istituto Nazionale dei Tumori, Fondazione Pascale, Napoli, Italy.
  • Department of Obstetrics and Gynecology, School of Medicine, Koc University, Istanbul, Türkiye.
  • Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy.

Abstract

BACKGROUND

Sentinel lymph node (SLN) mapping has increasingly replaced systematic lymphadenectomy in apparent uterine-confined endometrial cancer (EC). However, concerns persist regarding the risk of recurrence following nodal surgical de-escalation, particularly in patients with aggressive histologic subtypes. We aimed to evaluate the oncologic safety of SLN-based nodal de-escalation by analyzing recurrence patterns and recurrence-free survival in patients with apparent early-stage EC.

METHODS

We conducted a retrospective multi-institutional study including women with apparent uterine-confined EC who underwent primary surgery including SLN mapping, with or without pelvic and/or para-aortic lymphadenectomy. Patients were grouped according to nodal staging strategy: SLN-only, SLN plus pelvic lymphadenectomy (PLND), and SLN plus PLND plus para-aortic lymphadenectomy (PALND). The primary endpoints were progression-free survival (PFS) and patterns of recurrence.

RESULTS

We included 2123 patients from 15 centers in six countries. SLN-only staging was performed in 1,341 patients (63.2%), SLN+PLND in 483 (22.8%), and SLN+PLND+PALND in 299 (14.1%). With a median follow-up of 44.9 months (IQR 19.1-73.4), 121 recurrences were observed (5.6%). No statistically significant differences in PFS were observed among nodal staging groups. On multivariable Cox analysis, SLN-only staging was not associated with inferior PFS compared with SLN+PLND (HR 1.12, p=0.61), and the addition of PALND did not confer a significant benefit. Endometrioid high-grade histology, non-endometrioid high-risk histotypes, deep myometrial invasion, and lymphovascular space invasion were independently associated with recurrence. Isolated nodal relapse was uncommon (14.9%) and similarly distributed across groups. Exploratory molecular analysis did not show statistically significant differences in PFS across molecular subgroups, although expected survival trends were observed.

CONCLUSIONS

In apparent uterine-confined EC, no significant differences in recurrence or nodal relapse were observed across nodal staging strategies. These findings support the use of SLN mapping as an adequate staging approach within a biology-driven framework, although they should be interpreted in light of the retrospective design.

MeSH

Safety, Lymph Nodes, Lymph Node Excision, Neoplasms, Multiple Chronic Conditions, Cohort Studies, Sentinel Lymph Node, Lymph, Endometrial Neoplasms