Uterine Cancer Types: Endometrial Cancer

Endometrial cancer, also known as uterine lining cancer, is one of the most common types of gynecological cancers affecting women today. It originates from the endometrium, the inner lining of the uterus. Endometrial cancer primarily affects post-menopausal women, primarily due to the hormonal changes associated with it. Endometrial cancer is a growing cause for concern, with mortality rates increasing each year. Fortunately, endometrial cancer can be detected early due to clear and noticeable symptoms. This increases the chances of survival by enabling timely intervention.

Endometrial cancer was traditionally classified into 2 distinct types — type I and type II endometrial cancer.

Type I endometrial cancer is associated with elevated estrogen levels which disrupt the estrogen-progesterone balance in the body. This causes persistent stimulation of the endometrium, resulting in abnormal thickening of the uterine lining. Such uncontrolled proliferation greatly increases the risk of developing endometrial cancer. Type I endometrial cancer accounts for the majority of endometrial cancer cases and are typically less aggressive. It can often be detected early and is less likely to spread to other areas of the body.

Type II endometrial cancer is less prominently linked to estrogen exposure. While it only accounts for a small proportion of endometrial cancers, type II endometrial cancer is usually more aggressive. They are also often associated with poorer prognosis and are more likely to spread to other areas of the body.

Latest classification system

In 2023, a new classification was adopted internationally. This was a shift from looking at cancer cells under the microscope to grouping tumours by their genetic and molecular traits into four molecular subtypes. This classification is much better at predicting the behavior of the cancer and also helps with appropriate targeted therapy. A simplified classification with a description of each subtype is shown below:

• POLE mutation: Mutation in the POLE gene. Excellent prognosis and may not require treatment beyond surgery.
• Mismatch Repair Deficiency (MMRd): Moderate risk; strongly predicts a high response to immunotherapy.
• No Specific Molecular Profile (NSMP): Intermediate risk; typically respond well to hormonal therapies.
• P53 Abnormal: Mutation in the TP53 gene, which is responsible for stopping damaged cells from multiplying. These are typically fast growing aggressive tumours. The vast majority are clear cell carcinomas and carcinosarcomas and approximately 90% of serous tumours fall into this category. Patients diagnosed with this type of endometrial cancer require treatment with aggressive surgery, radiotherapy, intensive chemotherapy and possibly new targeted therapies.

Endometrioid carcinomas are the most common type of endometrial cancer and are categorized across all four molecular groups. Up to 60% are NSMP, with 25-30% being MMRd, 10% being POLE mutated and 5-10% being p53 abnormal. Additionally, findling an MMRd endometrioid cancer prompts testing the patient for Lynch syndrome, which is a hereditary condition which increases the risk of colon and uterine cancers.

The prognosis of endometrial cancer is closely linked to its subtype and the stage at which it is diagnosed. Generally, type I endometrial cancers and localized tumors (low stage endometrial cancer) have a better prognosis.

Experts from the American Cancer Society estimate that there are more than 600,000 survivors of endometrial cancer today. As reported by the Surveillance, Epidemiology, and End Results (SEER) database, the five-year relative survival rates for endometrial cancer estimated based on cases from 2014–2020 are:

The SEER database classifies five-year relative survival rates into three stages based on the extent of cancer spread.

In general, the outlook of endometrial cancer cases detected early is positive. The majority of such patients survive for more than five years.

Learn more: Uterine Cancer: Prognosis and Survival Rates

Endometrial cancer often presents clear symptoms and can be detected in the early stages. Common symptoms include:

• Abnormal vaginal bleeding/discharge
• Vaginal spotting
• Pelvic pain
• Weight loss

It is important to seek medical attention should you notice any of these symptoms to ensure timely intervention.

Learn more: Signs and Symptoms of Endometrial Cancer

The diagnostic process for endometrial cancer is essential in determining cancer severity, treatment options and prognosis. It involves a structured approach to help doctors identify the best treatment option.

Initial evaluation often involves the use of ultrasound. Transvaginal ultrasound (TVUS) is used to image the uterus. This helps to identify the presence of tumor growth or any abnormal thickening of the endometrium. This is typically followed by a biopsy, whereby a sample of uterine tissue is taken for microscopic analysis to confirm the existence of cancer. Further testing may also be carried out to assess the severity and extent of spread of the cancer.

Learn more: Diagnosing Uterine Cancer

Endometrial cancer is typically treated by surgery, most commonly via a hysterectomy. Depending on the severity of the cancer, the surgery may involve removing only the uterus or the uterus along with nearby structures.

It is also recommended that the fallopian tubes and ovaries be removed if the patient is post-menopausal. Although rare, the incidence of cancer of the fallopian tubes and ovaries rise after the menopause. Other treatment options include:

• Radiation therapy: May be performed post-surgery to kill any remaining cancer cells.
• Hormone therapy: Occasional role in treating advanced cases of NSMP.
• Chemotherapy: Performed post-surgery in cases where cancer is advanced or when there is a high risk of recurrence in early-stage cancer.
• Immunotherapy: Usually used to treat advanced or recurrent endometrial cancer. It can also be employed if the cancer has metastasized beyond the uterus.
• Targeted therapy: relies on the new molecular classification and is used in treatment against specific subtypes.

Treatment for endometrial cancer varies according to the severity of cancer (stage and grade) and individual patient factors. Hence, a personalized approach is important in optimizing treatment outcomes and minimizing side effects.

Learn more: Uterine Cancer Treatments

Understanding the risk factors associated with endometrial cancer is essential for early detection and prevention. Although the exact cause of endometrial cancer remains unclear, various factors have been linked to an increased risk of developing the disease. These include:

• Obesity: Having more fat increases estrogen levels in the body, increasing the risk of developing endometrial cancer.
• Reproductive factors: Early menarche, late menopause or nulliparity increases the risk of developing endometrial cancer.
• Age: Women who are older, especially those who have undergone menopause, are at a higher risk of developing endometrial cancer.
• Medical conditions: Certain medical conditions such as diabetes mellitus and polyendocrine metabolic syndrome (PMOS), formally called polycystic ovary syndrome, are associated with a greater risk of developing endometrial cancer.
• Genetics: Women with a family history of uterine cancer or lynch syndrome are more prone to developing endometrial cancer.

While there are no definitive methods of preventing endometrial cancer, certain measures can help to reduce the risk. These include:

• Maintaining a healthy diet
• Staying physically active
• Pregnancy
• Oral contraceptive pills

Understanding and addressing these risk factors can significantly aid in the prevention and early detection of endometrial cancer.