Statement by the Uterus Commission of the Arbeitsgemeinschaft Gynäkologische Onkologie [German Gynecological Oncology Group] (AGO) on the ESGO-ESTRO-ESP Guideline 2025.

The ESGO-ESTRO-ESP guideline 2025 integrates the molecular classification into prognostic risk stratification and therapeutic decisions for patients with endometrial cancer (EC). In particular, a refined stratification of the molecular subgroup No-Specific-Molecular-Profile (NSMP) has been recently introduced to better reflect its pronounced prognostic heterogeneity. Retrospective analyses by Jamieson et al. and Vermij et al. demonstrate that histological tumor grade and immunohistochemical estrogen receptor expression represent independent prognostic factors within the NSMP subgroup, allowing for the identification of a large subgroup with an excellent prognosis and a small subgroup with a poor prognosis. Additional exploratory post hoc analyses suggest a potential differential benefit of adjuvant chemotherapy in ER-negative NSMP EC. However, these observations remain hypothesis-generating and lack prospective validation. In addition, the exact cut-off for ER-positivity remains unclear. The ESGO guideline defines prognostic risk groups according to the estimated 5-year risk of recurrence and derives recommendations for adjuvant therapy accordingly. Key randomized trials, including PORTEC-1, PORTEC-2, PORTEC-3, GOG-249 and GOG-258, are incorporated alongside molecular subgroups, whose biological characteristics increasingly inform treatment intensity. In contrast, the German S3 guideline adopts a more conservative methodological approach, incorporating molecular markers primarily as supportive information, particularly in the absence of prospective evidence guiding specific therapeutic decisions. With respect to surgical management in early-stage disease (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] I-II), both guidelines show substantial agreement, especially regarding the preference for minimally invasive surgery and the avoidance of unnecessary radicality. Differences mainly relate to the indication for sentinel lymph node staging. This statement aims to provide a balanced contextualization of these conceptual differences and to support an informed discussion of current international developments.