Endometrial cancer

What is uterine body cancer or endometrial cancer ?

Tumors of the uterus can originate from the cervix, which is the lowest part of the uterus, or the body of the uterus, which includes the regions above the cervix.

Uterine tumors can be either benign or malignant and primarily affect the body of the uterus.

The uterus, a pear-shaped organ located in the pelvis, consists of an inner layer called the endometrium (involved in menstruation and pregnancy) and an outer muscular layer, the myometrium, which plays a key role during childbirth.

In 2020, it is estimated that approximately 417,000 new cases of endometrial cancer were diagnosed worldwide, with 97,000 deaths attributed to this disease.

This type of cancer is the sixth most common cancer among women globally, accounting for about 3% of all female cancers (source: World Health Organization).

The incidence of endometrial cancer increases with age, with most cases being diagnosed after menopause, typically between the ages of 60 and 70.

Around 75% of cases occur after the age of 50, and the average age at diagnosis is between 60 and 70 years. The prognosis is favorable when the cancer is detected at an early stage, often due to symptoms such as abnormal vaginal bleeding. Early detection frequently allows for more effective treatment and a better quality of life after treatment.

Causes and risk factors

Endometrial cancers are associated with several risk factors :

• Age: the risk increases with advancing age.
• Obesity : this is the factor most closely linked to this cancer. In the United States, 75% of endometrial cancer cases are attributed to obesity, with the risk increasing up to 50% in cases of severe obesity.
• Type 2 diabetes : double the risk compared to non-diabetic women.
• Prolonged exposure to estrogen : Factors such as early puberty, late menopause, absence of pregnancy, or hormone treatments (estrogen alone or tamoxifen) contribute to the risk.
• Polycystic ovary syndrome (PCOS) : A common hormonal disorder that can cause metabolic issues and increase the risk.
• Genetic predisposition : Mutations, particularly in Lynch syndrome, elevate the risk.
• Family history : Having a first-degree relative with this cancer doubles the risk.

Conversely, several factors protect against endometrial cancer :

• Maintaining a normal weight or losing weight in cases of obesity.
• Pregnancy and breastfeeding, which reduce estrogen exposure.
• Exposure to progesterone through regular menstrual cycles, progestin-based oral contraceptives, a progestin-releasing intrauterine device (IUD), or hormone replacement therapy during menopause.

These risk and protective factors should be considered to better prevent and manage the risk of endometrial cancer.

Screening

Endometrial cancer is not subject to generalized screening. However, regular gynecological exams and vigilance regarding abnormal vaginal bleeding are essential for early detection.

Detection is carried out using the following methods :

• Transvaginal ultrasound : Measures the thickness of the endometrium and identifies potential abnormalities, particularly useful after menopause or in high-risk patients.
• Endometrial biopsy : Performed via aspiration or curettage, this procedure diagnoses most cancers.
• Specific monitoring : For patients with Lynch syndrome, annual ultrasound and biopsy are recommended starting at age 35.

Symptoms

The main symptoms are :

• Abnormal vaginal bleeding : - Before menopause: often caused by fibroids. - After menopause : metrorrhagia occurs in 80% of diagnosed women.
• Other signs : pvaginal discharge (leukorrhea), pelvic pain, pain during intercourse (dyspareunia), difficulties or pain during urination, and, less frequently, the presence of a palpable mass.

These symptoms should be investigated, even though benign causes are possible (fibroids, infections). Early detection and management increase the chances of successful treatment.

Diagnosis

When endometrial cancer is suspected, the gynecologist explores the symptoms experienced, personal and family medical history, and risk factors (e.g., obesity, hypertension, late menopause). A complete clinical examination is conducted, including a vaginal and rectal exam, a vaginal smear, and a transvaginal ultrasound.

If necessary, additional tests such as a biopsy, hysteroscopy, or colposcopy are performed :

• Diagnostic hysteroscopy : allows visualization of lesions, guides biopsies, and confirms the malignant nature (histological analysis).
• Types of tumors : - Endometrioid adenocarcinoma (80% of cases) generally occurs after menopause and is associated with a better prognosis. - Non-endometrioid cancers (20%) affect older women, with a less favorable prognosis.
• Tumor grades : - Grade 1: well-differentiated cells, limited proliferation. - Grade 3: poorly differentiated cells, aggressive proliferation.

An imaging assessment (MRI, CT scan) evaluates the extent of the disease (lymph nodes, metastases) and determines its stage according to the TNM classification :

• Stage 1 : limited to the endometrium.
• Stage 2 : involvement of the cervix.
• Stage 3 : extension beyond the uterus (pelvic region).
• Stage 4 : involvement of distant organs (e.g., bladder, rectum).

In some patients (e.g., Lynch syndrome), genetic tests (microsatellite instability - MSI) determine if immunotherapy is possible. MSI tumors, resulting from a deficiency in the DNA repair system, may benefit from these innovative treatments.

The determination of the stage and grade guides the treatment and helps predict the disease's progression.

Treatments

The treatment of endometrial cancer is becoming increasingly personalized and tailored to each patient.

It depends on several factors, including the nature and grade of the cancer cells, the MSI status (microsatellite instability), the stage of the disease, and its location.

The management plan is discussed in a Multidisciplinary Tumor Board (MTB), bringing together various specialists (oncologists, surgeons, radiotherapists, etc.) to define the optimal therapeutic pathway.

The available treatments are :

• Surgery : often the initial treatment, performed by laparoscopy or robot-assisted surgery. It includes the removal of the uterus, cervix, ovaries, and sentinel lymph nodes. Ovarian preservation may be considered in some early cases.
• Radiotherapy : used as adjuvant therapy after surgery or alone in certain cases. It can be external or vaginal brachytherapy.
• Chemotherapy : mainly prescribed for high-grade tumors or advanced stages. It works by destroying cancer cells, although it may cause side effects.
• Hormone therapy : used to block the action of estrogen, which is involved in certain cancers, especially in obese women or in the case of recurrence.
• Immunotherapy : particularly effective for cancers with microsatellite instability (MSI). It stimulates the immune system to attack cancer cells.

Immune therapies using checkpoint inhibitors represent a major breakthrough, blocking the mechanisms that allow cancer cells to escape the immune system. In addition, clinical trials are ongoing to explore new therapeutic approaches, further optimizing treatment.

Each step of the treatment is explained during an "initial consultation," allowing the patient to understand their pathway, which may include multiple types of treatments depending on the progression of the disease.