Endometrial Carcinoma: Causes, Symptoms & Treatment

What is Endometrial Carcinoma?

Endometrial carcinoma (also called uterine cancer or cancer of the womb lining) is a malignant tumor originating from the cells of the endometrium – the inner lining of the uterus. It is the most common gynecological malignancy in Western countries and predominantly affects postmenopausal women, with an average age of diagnosis around 65 years.

There are two main subtypes: the estrogen-dependent Type I (endometrioid carcinoma, more common, better prognosis) and the estrogen-independent Type II (e.g., serous or clear cell carcinoma, more aggressive, poorer prognosis).

Causes and Risk Factors

Prolonged, unopposed estrogen exposure (estrogen dominance) plays a central role in the development of the disease. Additional risk factors include:

• Obesity: Adipose tissue produces estrogens, increasing cancer risk
• Type 2 diabetes and metabolic syndrome
• Late menopause (after age 55)
• Nulliparity (never having given birth)
• Polycystic ovary syndrome (PCOS)
• Long-term use of tamoxifen (in breast cancer treatment)
• Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) – a hereditary condition significantly increasing risk
• No or low use of oral contraceptives

Symptoms

An early and characteristic symptom of endometrial carcinoma is abnormal vaginal bleeding, especially after menopause (postmenopausal bleeding). Any vaginal bleeding after menopause should be evaluated by a physician promptly.

• Postmenopausal vaginal bleeding (most common first symptom)
• Irregular or heavy menstrual bleeding in premenopausal women
• Watery or blood-tinged vaginal discharge
• Pelvic or lower abdominal pain (more common in advanced stages)
• Pain during intercourse
• Unintentional weight loss and fatigue (in later stages)

Diagnosis

Diagnosis of endometrial carcinoma involves several steps:

Gynecological Examination

A thorough clinical examination provides initial evidence of uterine abnormalities.

Transvaginal Ultrasound

Transvaginal ultrasound is used to measure the thickness of the endometrial lining. In postmenopausal women, an endometrial thickness greater than 5 mm is considered suspicious and warrants further investigation.

Endometrial Biopsy and Hysteroscopy

An endometrial biopsy (tissue sampling from the uterine lining) is the most important diagnostic procedure. It is often performed alongside hysteroscopy (direct visualization of the uterine cavity) and fractional curettage to obtain tissue for histological analysis.

Imaging Studies

To determine the tumor stage and extent of spread, MRI (magnetic resonance imaging), CT (computed tomography), or PET-CT scans are used to assess lymph nodes and adjacent organs.

Staging

Staging follows the FIGO classification (International Federation of Gynecology and Obstetrics), ranging from Stage I (confined to the uterus) to Stage IV (distant metastases).

Treatment

Treatment of endometrial carcinoma depends on the stage, histology, age, and general health of the patient.

Surgery

Surgical treatment is the standard therapy and typically involves a total hysterectomy (removal of the uterus) along with bilateral removal of the ovaries and fallopian tubes (bilateral salpingo-oophorectomy). Pelvic and para-aortic lymph node dissection may also be performed. The procedure is often carried out minimally invasively (laparoscopic or robotic approach).

Radiation Therapy

Radiation therapy is used as adjuvant treatment after surgery, either as brachytherapy (internal vaginal radiation) or external pelvic beam radiation, to reduce the risk of recurrence.

Chemotherapy

For advanced or recurrent tumors, a platinum-based chemotherapy regimen (e.g., carboplatin and paclitaxel) is used.

Hormone Therapy

In estrogen-dependent tumors and in patients wishing to preserve fertility, progestin therapy may be considered.

Targeted Therapy and Immunotherapy

Newer approaches include targeted agents such as pembrolizumab (a checkpoint inhibitor) for mismatch repair-deficient (dMMR) tumors, and lenvatinib in combination with pembrolizumab for advanced disease.

Prognosis

When diagnosed early, the prognosis for endometrial carcinoma is generally favorable. The 5-year survival rate for Stage I exceeds 90%. However, in advanced stages (III and IV), survival rates decline significantly. Regular follow-up examinations after completing therapy are essential.

Prevention

There is no definitive method to prevent endometrial carcinoma entirely. However, the following measures can help reduce the risk:

• Weight management and a healthy diet
• Regular physical activity
• Adequate management of diabetes and metabolic syndrome
• Use of combined oral contraceptives where indicated
• Genetic counseling for individuals with suspected Lynch syndrome

References

1. Colombo N et al. - ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up. Annals of Oncology, 2016; 27(1): 16–41.
2. World Health Organization (WHO) - Classification of Tumours: Female Genital Tumours, 5th Edition, 2020.
3. National Comprehensive Cancer Network (NCCN) - Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 2024. Available at: nccn.org.