Endometrial Carcinoma Clinical Practice Guidelines (ESGO/ESTRO/ESP, 2021)

European Society of Gynaecological Oncology, European Society for Radiotherapy and Oncology, and European Society of Pathology

This is a quick summary of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference.

January 29, 2021

The guideline update on endometrial carcinoma was released in January 2021 by the European Society of Gynaecological Oncology, European Society for Radiotherapy and Oncology, and European Society of Pathology.[1]

Staging and Risk Stratification

Histopathologic type, grade, myometrial invasion, and lymphovascular space invasion (LVSI; designated as no/focal/substantial) should be recorded in all patients with endometrial carcinoma.

Molecular classification (eg, through analysis of POLE mutation, abnormal p53, microsatellite instability [MSI], mismatch repair deficiency [MMRd]) is encouraged in all cases, especially high-grade tumors. POLE mutation analysis may be omitted in low-risk and intermediate-risk endometrial carcinoma with low-grade histology.

Patients are assigned to prognostic risk groups (low, intermediate, high-intermediate, high, advanced metastatic) on the basis of standard staging criteria or with molecular classification.

Treatment of Early-Stage Disease

Minimally invasive surgery is the preferred surgical approach, including patients with high-risk endometrial carcinoma.

Any intra-peritoneal tumor spillage, including tumor rupture or morcellation (including in a bag), should be avoided. If vaginal extraction risks uterine rupture, other measures should be taken (eg, mini-laparotomy, use of endobag).

Metastases outside the uterus and cervix (excluding lymph node metastases) are relative contraindications for minimally invasive surgery.

Standard surgery is total hysterectomy with bilateral salpingo-oophorectomy without vaginal cuff resection.

Staging infracolic omentectomy should be performed in clinical stage I serous endometrial carcinoma, carcinosarcoma, and undifferentiated carcinoma. It can be omitted in stage I clear cell and endometrioid carcinoma.

Surgical re-staging can be considered in previously incompletely staged patients with high- intermediate-risk/high-risk disease if the outcome might have an implication for adjuvant treatment strategy.

Lymph node staging

Sentinel lymph node biopsy (SLNB) can be considered for staging purposes in patients with low-risk/intermediate-risk disease. It can be omitted in cases without myometrial invasion. Systematic lymphadenectomy is not recommended in this group.

Surgical lymph node staging should be performed in patients with high-intermediate risk/high-risk disease. SLNB is an acceptable alternative to systematic lymphadenectomy for lymph node staging in stage I/II.

When a systematic lymphadenectomy is performed, pelvic and para-aortic infrarenal lymph node dissection is suggested.

Presence of both macrometastases and micrometastases (<2 mm, pN1[mi]) is regarded as a metastatic involvement.

If pelvic lymph node involvement is found intraoperatively, further systematic pelvic lymph node dissection should be omitted. However, debulking of enlarged lymph nodes and para-aortic staging can be considered.

Ovarian preservation and salpingectomy in stage I/II

Ovarian preservation can be considered in premenopausal patients aged <45 years with low-grade endometrioid endometrial carcinoma with myometrial invasion <50% and no obvious ovarian or other extra-uterine disease. However, salpingectomy is recommended.

Ovarian preservation is not recommended for patients with family history involving ovarian cancer risk (eg, BRCA mutation, Lynch syndrome).

Surgery for stage II disease

Total hysterectomy with bilateral salpingo-oophorectomy and lymph node staging is the surgical standard of care in patients with stage II endometrial carcinoma.

More extensive procedures should be performed only if required to achieve clear surgical margins.

Medically unfit patients

Vaginal hysterectomy, with bilateral salpingo-oophorectomy if feasible, can be considered in patients unfit for the recommended standard surgical therapy.

Definitive radiotherapy can be considered for primary tumors where surgery is contraindicated for medical reasons.

In medically unfit patients unsuitable for curative surgery or radiotherapy, systemic treatment (including hormonal therapy) can be considered.

Fertility preservation

Fertility-sparing treatment should be considered only in patients with atypical hyperplasia/endometrioid intra-epithelial neoplasia or grade 1 endometrioid endometrial carcinoma without myometrial invasion and without genetic risk factors.

Patients who are candidates for fertility-preserving treatment must be referred to specialized centers.

Patients must be informed that fertility-sparing treatment is not a standard treatment and must be willing to accept close follow-up and the need for future hysterectomy in case of failure of treatment and/or after pregnancies.

Adjuvant treatment

For patients with low-risk endometrial carcinoma, no adjuvant treatment is recommended

For patients with intermediate-risk disease, adjuvant brachytherapy can be recommended to decrease vaginal recurrence but may be omitted, especially in patients aged <60 years.

For p53-abnormal carcinomas restricted to a polyp or without myometrial invasion, adjuvant therapy is generally not recommended.

For patients with high-intermediate risk cN0/pNx (lymph node staging not performed), adjuvant external beam radiation therapy (EBRT) is recommended, especially for substantial LVSI and/or for stage II; additional adjuvant chemotherapy can be considered, especially for high-grade and/or substantial LVSI; adjuvant brachytherapy alone can be considered for high-grade LVSI negative and for stage II grade 1 endometrioid carcinomas.

For patients with high-risk disease, EBRT with concurrent adjuvant chemotherapy or sequential chemotherapy and radiotherapy is recommended. Chemotherapy alone is an alternative option. Carcinosarcomas should be treated as high-risk carcinomas, not as sarcomas.

Treatment of Advanced Disease

In stage III and IV endometrial carcinoma (including carcinosarcoma), surgical tumor debulking including enlarged lymph nodes should be considered when complete macroscopic resection is feasible with an acceptable morbidity and quality of life profile, following full preoperative staging and discussion by a multidisciplinary team.

Primary systemic therapy should be used if upfront surgery is not feasible or acceptable. In cases of a good response to systemic therapy, delayed surgery can be considered.

Only enlarged lymph nodes should be resected. Systematic lymphadenectomy is not recommended.

For unresectable tumors, multidisciplinary team discussion should consider definitive radiotherapy with EBRT and intrauterine brachytherapy, or neoadjuvant chemotherapy prior to surgical resection or definitive radiotherapy, depending on response. Image-guided brachytherapy is recommended to boost intrauterine, parametrial, or vaginal disease. Chemotherapy should be considered after definitive radiotherapy

Residual pelvic or para-aortic lymph node disease following surgery should be treated with a combination of chemotherapy and EBRT or chemotherapy alone. EBRT should be delivered to pelvis and para-aortic nodes with dose escalation to involved nodes using an integrated or sequential boost.

For patients with residual pelvic disease following surgery, an individualized approach with radiotherapy and/or chemotherapy should be considered by a multidisciplinary team.

For more information, see Endometrial Carcinoma. For more Clinical Practice Guidelines, please go to Guidelines.

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