Guideline Essentials: 2022 ESMO Recommendations on Endometrial Cancer

Introduction

In 2022, the European Society for Medical Oncology (ESMO) published guidance on the diagnosis, staging, treatment, and follow up of patients with endometrial cancer.

This specialist Guidelines overview for secondary care oncologists provides a summary of the key recommendations on the management of local, recurrent, and metastatic endometrial cancer, and incorporates insights on diagnosis, molecular biology, treatment options, and follow up. 

Please refer to the full ESMO guideline for all of the recommendations, rationale, and background information. 

Key Takeaways from the Guideline

• Grade tumours according to the International Federation of Gynaecology and Obstetrics (FIGO) criteria
• Perform preoperative staging to define surgical management
• Determine an integrated molecular classification for all patients, based upon:
  • polymerase epsilon (POLE) status
  • mismatch repair (MMR) status
  • p53 status
• Standard surgery in early-stage EC is hysterectomy with bilateral salpingo–oophorectomy
• Sentinel lymph node biopsy and/or systemic lymphadenectomy can be performed, dependant upon lymph node staging and EC risk stage; this can be omitted in patients who have low stage (1) and grade (1/2) tumours, but is recommended for all other patients
• Substantial lymphovascular space invasion (LVSI) greatly increases the risk of recurrence and death
• Adjuvant treatment for low-risk EC is not recommended, except as part of a clinical trial in patients who have stage III polymerase epsilon-ultramutated cancers
• Adjuvant vaginal brachytherapy (VBT) and external beam radiation therapy (EBRT) can be used in intermediate-risk, high–intermediate-risk and high-risk EC, dependent upon EC stage and pathology of regional lymph nodes 
• Recurrent and metastatic disease should be managed by a multidisciplinary team in specialised centres, with decisions informed by the patient’s condition, stage of EC, molecular classification, and previous therapies.

Staging Investigations

• Include the following preoperative assessments:
  • clinical and gynaecological examination
  • transvaginal ultrasound
  • pelvic magnetic resonance imaging
  • full blood count
  • liver and kidney function profiles
• Consider thoracic and abdominal computed tomography (CT) scan and/or fluorodeoxyglucose–positron emission tomography (PET)–CT for patients at high risk of extrapelvic disease
• Biopsy or dilatation and curettage are suitable procedures for taking endometrial tissue samples—for example, pipelle biopsy in an office setting, or hysteroscopy and biposy in theatre.

Diagnosis, Pathology, and Molecular Biology

• Determine the following:
  • histological type
  • FIGO grade
  • myometrial invasion
  • extent of LVSI—focal/substantial
• Carry out molecular classification for p53 and MMR proteins (MLH1, PMS2, MSH2, MSH6) with targeted POLE hotspot analysis.

Management of Local and Locoregional Endometrial Cancer

Table 1: Surgical Management of Local and Locoregional Disease

Table 2: Adjuvant Therapy for Local and Locoregional Disease

Locoregional Recurrent Endometrial Cancer Treatment Options

• For patients who received only VBT:
  • EBRT
  • optional systemic therapy
• For patients following primary surgery alone:
  • EBRT and VBT
  • consider adding systemic therapy to salvage radiotherapy (RT)
• For patients who received prior RT:
  • debulking surgery, provided that the benefits outweigh the risks
  • consider complementary systemic treatment after surgery.

Recurrent/Metastatic Endometrial Cancer

• Patients with recurrent/metastatic EC should be treated by a specialised multidisciplinary team
• Treatment is determined by the patient’s age and overall health, extent of the EC, previous therapies, and molecular characteristics of the EC.

First-line Treatments

• First-line chemotherapy treatment is carboplatin (area under the curve 5–6) plus paclitaxel 175 mg/m² every 21 days for six cycles
• For low-grade carcinomas with endometrioid histology or low-volume or indolent disease, consider hormone therapy:
  • progestins (medroxyprogesterone acetate 200 mg or megestrol acetate 160 mg are recommended)
  • aromatase inhibitors
  • tamoxifen
  • fulvestrant.

Second-Line Treatments 

• Consider pembrolizumab–lenvatinib
• Consider rechallenge with platinum-based therapy
• No chemotherapy treatment is regarded as standard-of-care; however, doxorubicin and weekly paclitaxel are considered most active
• For patients with microsatellite instability-high/MMR deficient EC, consider dostarlimab monotherapy following platinum-based treatment failure.

Follow Up

• For all EC survivors, promote healthy lifestyle choices, such as weight management, regular exercise, and healthy diet
• Educate patients about concerning signs and symptoms.

Low-risk Endometrial Cancer

• For the first 2 years, offer physical and gynaecological examination every 6 months, then follow-up annually until 5 years; telephone consultations are an option.

High-risk Endometrial Cancer

• For the first 3 years, offer physical and gynaecological examination every 3 months then 6-monthly until 5 years
• Consider CT scan or PET–CT, especially if node extension was present.