ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025

Key guideline recommendations

1. Planning of staging and treatment should be made in a multidisciplinary setting (generally a tumour board) and based on precise knowledge of prognostic and predictive factors for outcome, morbidity and quality of life; treatment, especially in high-risk or advanced disease, should take place in a specialised centre.

   V, A

2. To identify patients at risk of Lynch syndrome, immunohistochemistry for mismatch repair proteins (with MLH1 promoter methylation analysis when MLH1 alone or MLH1 with PMS2 expression is lost) is the preferred option and should be done for all patients with endometrial carcinoma.

   III, A

3. In carriers of Lynch syndrome, endometrial surveillance should generally start at age 30 with annual transvaginal ultrasound and annual or biennial biopsy until hysterectomy; prophylactic hysterectomy and bilateral salpingo-oophorectomy by minimally invasive surgery should be offered after completion of childbearing, preferably before age 40 with MLH1, MSH2 or MSH6 mutations and at the menopause with PMS2 mutations.

   IV, B

4. Molecular classification (POLEmut, MMRd, NSMP and p53abn) should be done for all types of endometrial carcinoma; oestrogen receptor testing by immunohistochemistry is recommended in all endometrial carcinomas.

   IV, A

5. Standard surgery for stage I and II disease is total hysterectomy with bilateral salpingo-oophorectomy and lymph node staging (II, A for stage I and IV, B for stage II). Minimally invasive surgery is the preferred approach, including for high-risk disease (I, A), and any intraperitoneal tumour spillage, including morcellation, should be avoided (III, A).

   II, A; I, A

6. Sentinel lymph node biopsy should be done for staging in all patients with presumed uterus-confined disease; indocyanine green with cervical injection is the preferred technique; if no sentinel node is found on one side, side-specific systematic lymphadenectomy should be done in high–intermediate or high risk; all sentinel nodes should undergo ultrastaging.

   II, A

7. Ovarian preservation can be considered in premenopausal patients under 45 with FIGO 2023 IA1 or IA2 and a low risk by molecular classification, with bilateral salpingectomy; but not in carriers of BRCA mutations or Lynch syndrome.

   IV, B

8. Low risk: no adjuvant therapy is recommended. Intermediate risk: adjuvant vaginal brachytherapy should be considered (I, A), and no adjuvant therapy is also an option (III, C), especially under 60 or with low grade (II, A).

   II, A; I, A

9. High–intermediate risk: external beam radiotherapy is recommended for optimal pelvic control (II, A); vaginal brachytherapy is an alternative, especially after nodal staging with pN0 (II, B).

   II, A; II, B

10. High risk: external beam radiotherapy with concurrent and adjuvant chemotherapy (I, A) or sequential chemotherapy and radiotherapy (I, B) is recommended; chemotherapy with or without brachytherapy is an alternative (I, B). In stage IIIm and IVAm MMRd disease, adjuvant chemotherapy combined with an immune checkpoint inhibitor (with or without external beam radiotherapy) should be considered (II, B).

    I, A; II, B

11. First line for advanced or recurrent disease: in MMRd, an immune checkpoint inhibitor (such as dostarlimab, durvalumab or pembrolizumab) with carboplatin–paclitaxel, followed by immune checkpoint inhibitor maintenance, should be offered (I, A). In non-MMRd with rapidly growing or symptomatic disease, carboplatin–paclitaxel (I, A); adding an immune checkpoint inhibitor with maintenance (such as dostarlimab or pembrolizumab), or maintenance with durvalumab and olaparib, can be considered (I, B). The standard regimen is 6 cycles of carboplatin–paclitaxel (I, A).

    I, A; I, B

12. In low-grade, oestrogen receptor-positive, low-volume or asymptomatic tumours, or slowly growing recurrences, endocrine therapy is the preferred systemic therapy, and progestogens (medroxyprogesterone or megestrol) are recommended (III, A); alternatives include aromatase inhibitors and tamoxifen (IV, C).

    III, A

13. Second line after platinum in immunotherapy-naive patients: in MMRd, immune checkpoint inhibitor monotherapy (such as dostarlimab or pembrolizumab) is the preferred option (III, A), and pembrolizumab + lenvatinib can be considered (I, B); in non-MMRd, pembrolizumab + lenvatinib should be offered (I, A). After first-line immunotherapy: a platinum combination, doxorubicin, weekly paclitaxel or endocrine therapy (IV, B).

    I, A; III, A

14. Patients should be informed about follow-up: its main aims are psychosocial support and detection of health problems, and there is no evidence that follow-up visits improve overall survival; follow-up should be personalised to individual factors (such as molecular classification, treatments given, side effects and needs).

    V, A

Study population

Clinical significance and place in guidelines

Limitations