The molecular classification has now become a fundamental component of the current Association of the Scientific Medical Societies in Germany (AWMF) S3 guidelines [1] and the European Society of Gynaecological Oncology, European Society for Radiotherapy and Oncology, European Society of Pathology (ESGO-ESTRO-ESP) guidelines [2] and forms the basis for recommendations on adjuvant therapy of endometrial cancer. It integrates clinical risk factors and molecular subgroups. In particular, the ESGO-ESTRO-ESP guidelines 2025 consistently derives its therapy recommendations from the classification into risk groups, whereas the current consultation draft of the AWMF S3 guidelines “Diagnostics and therapy of endometrial carcinoma” primarily uses molecular classification for the diagnosis and individualized prognosis. Key findings regarding adjuvant therapy are based on the results of the “Postoperative radiation therapy in endometrial cancer” (PORTEC) study series (1–4). In addition to establishing the role of postoperative radiotherapy for local control, these studies also demonstrated the added benefit of concomitant chemotherapy for a subgroup of patients. The results of the PORTEC 4a study were published in full earlier this year. Substantial improvements in adjuvant systemic therapy for high-risk patients with postoperative residual tumor and for primarily metastasized patients have been demonstrated in several studies through the use of immune checkpoint inhibitors. Comparable data supporting their use in the adjuvant high-risk setting without residual tumor are still lacking and were therefore not considered in the current AWMF S3 guidelines. Based on the consultation draft of the AWMF S3 guidelines this article aims to outline the indications as well as the available options for adjuvant therapy depending on the respective risk group.
