Endometrial Cancer

Endometrial cancer is a type of cancer that begins in the endometrium, the inner lining of the uterus. The uterus is the hollow, pear-shaped pelvic organ where fatal development occurs. Endometrial cancer is the 6th most commonly occurring cancer in women and the 15th most common cancer overall. There were more than 417,000 new cases of endometrial cancer in 2020 worldwide [1]. Most patients diagnosed with endometrial cancer are postmenopausal with a median age of 60 years at diagnosis.  

A risk factor leading to endometrial cancer includes having had breast, or ovarian cancer in the past. Other risk factors associated with endometrial cancer include being overweight/obesity, age (>50 years), and factors affecting the balance of female hormone levels. Endometrial cancer is predominantly sporadic caused by random mutations in the genes throughout an individual’s life. However, approximately 5% of endometrial cancer is due to hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. People with Lynch syndrome have a high- risk of developing endometrial cancer [2].

Endometrial cancer is divided into different types based on the characteristics of the tissue tumour samples. The majority of endometrial cancer cases exhibit either endometrioid (70%–80% of cases) or serous (10% of cases) characteristics. There are other less common types of endometrial cancer including clear cell carcinoma and, carcinosarcoma (formerly known as malignant mixed Mullerian tumours (MMMTs)). Serous carcinoma, clear cell carcinoma, and carcinosarcoma are considered to be high-risk tumours and generally exhibit aggressive behaviour and poor prognosis [4].

Furthermore, endometrial cancer is categorized into four stages (1-4) depending on the extent of the disease. The stage describes where the cancer is located and whether it has spread to other parts of the body.  

Stage 1: the cancer is found only in the uterus.

Stage 2: the tumor has spread beyond the uterus but is still in the pelvis.

Stage 3: the cancer is in the abdomen and possibly in the nearby lymph nodes.

Stage 4: The cancer has spread to rectum, bladder, lungs, or bones [5].  

Approximately 70% of the patients are diagnosed with stage 1 endometrial cancer due to the presence of clear symptoms. In patients with tumors localized to the uterus the 5-year survival rate is ≥ 95%, but decreases dramatically when the disease has escaped the uterus, with rates of 69% in patients with regional metastasis and 17% in those with distant metastatic disease [4]. Endometrial cancer can also be divided into 3 different grades. The grade describes how much cancer cells resemble healthy cells under a microscope. If the cancer cells look similar to healthy tissue, it is called "well differentiated" or a "low grade tumour." However, when the cancerous cells look very different from healthy tissue, the tumour is then called "poorly differentiated" or a "high-grade tumour" [4, 6].

Treatment of endometrial cancer can vary depending on the patient’s general health and age as well as the type, stage, and grade of the disease. Surgery is the primary treatment of choice in patients with endometrial cancer at all stages if there is no contradiction for performing it. Standard surgery requires a total hysterectomy, bilateral salpingo-oophorectomy, and lymph node evaluation. Total hysterectomy removes the uterus and cervix, and bilateral salpingo-oophorectomy removes the fallopian tubes and ovaries.  

Patients with stage 1 cancer are recommended to receive merely surgery. However, some patients at this stage might be recommended to receive radiation therapy following surgery to lower the risk of the cancer returning. Choice of treatment following surgery depends on various factors such as: age, cancer grade, how far the tumour extends into the muscle layer of the uterus (if at all) and whether there are tumour cells in the blood vessels or lymph vessels outside of the tumour. Vaginal brachytherapy and external beam radiation therapy are two common types of radiation therapy options for treatment of endometrial cancer. In vaginal brachytherapy, a small applicator is inserted in the vagina that delivers radiation directly to the targeted area. External beam radiation therapy delivers tightly targeted radiation beams from outside the body to the tumour site.

Majority of the patients with stage 2 endometroid cancer are recommend receiving surgery followed by radiation therapy.  

Patients with stage 3 and 4 are mostly treated with combination of surgery, radiotherapy, and systemic therapy. Systemic therapy is a type of treatment that travels through the bloodstream and targets the entire body. Either chemotherapy or hormone therapy might be used as systemic treatment for such patients. However, hormone therapy is only considered for patients with slow-growing tumours.

Endometrial cancer can sometimes develop in young women of child-bearing age. In such cases, surgery is still the recommended treatment. However, if the patients are at low-risk and choose fertility preservation after careful counselling, hormone therapy can be considered as an alternative.

If the cancer returns after initial therapy the choice of treatment depends on the location of the tumour and prior therapy. Patients who experience return of their cancer locally, meaning in the vagina, pelvis, and abdomen, will receive radiation therapy if they have not received it in their initial treatment. However, patients with prior radiation therapy are recommended to receive systemic therapy with or without radiation therapy. Radiation therapy in this context does not have curative role and is merely used to relieve the symptoms. There is also possibility that the cancer returns to other areas of the body a condition known as metastasis. Surgery of the tumour in metastatic areas, radiation therapy and systemic therapy are the recommended options. Furthermore, There are some new systemic treatment options such as targeted therapy and immunotherapy (e.g., checkpoint inhibitors) for patients with endometrial cancer expressing certain biomarkers in case of recurrence or metastasis on chemotherapy[2, 5].  

1. Endometrial cancer statistics. Available from: https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/.

2. Endometrial Cancer. BMJ Best Practice 2022; Available from: https://bestpractice.bmj.com.

3. Signs and Symptoms of Endometrial Cancer. Available from: https://www.cancer.org.

4. Yen, T.T., et al., Molecular Classification and Emerging Targeted Therapy in Endometrial Cancer. Int J Gynecol Pathol, 2020. 39(1): p. 26-35.

5. Endometrial Cancer. NCCN guideline for patients, 2021.

6. Uterine Cancer: Stages and Grades.

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