Endometrial Cancer

Endometrial cancer is a malignant neoplasm arising from the endometrial lining of the uterus and is one of the most common gynecological malignancies in women. It predominantly affects postmenopausal women, although it may occur in younger women with specific risk factors. Adenocarcinoma is the most common histological subtype. Early recognition and treatment are important because many cases present at an early stage and have a favorable prognosis when appropriately managed.

Epidemiology

Endometrial cancer is primarily a disease of older women and is most commonly diagnosed after menopause. The incidence is increasing globally, partly due to rising rates of obesity and diabetes mellitus. Most cases are diagnosed at an early stage because abnormal uterine bleeding often prompts medical evaluation.

Risk factors

Risk factors for endometrial cancer include:

• Obesity.

• Diabetes mellitus.

• High-fat diet.

• Early age at menarche.

• Nulliparity.

• Late age at menopause.

• Advanced age.

• Use of tamoxifen.

Pathophysiology

Endometrial cancer develops from malignant transformation of the endometrial glandular epithelium. Progressive cellular atypia and uncontrolled proliferation lead to the formation of invasive carcinoma. The disease may initially remain confined to the endometrium but can subsequently invade the myometrium, cervix, regional lymph nodes, and distant organs if left untreated.

Clinical presentation

The clinical presentation varies according to age, menopausal status, and disease stage. Abnormal uterine bleeding is the most common presenting symptom. Postmenopausal bleeding should always raise suspicion for endometrial malignancy until proven otherwise.

Symptoms

Postmenopausal women

• Abnormal uterine bleeding.

• Postmenopausal vaginal bleeding.

Premenopausal women

• Irregular vaginal bleeding.

• Intermenstrual bleeding.

• Abnormal vaginal discharge.

• Pain during sexual intercourse.

• Unexpected weight loss.

Advanced disease

• Pelvic pain.

• Constitutional symptoms including weight loss.

• Symptoms related to metastatic disease.

Clinical signs

Clinical findings may include:

• Abnormal uterine bleeding observed during examination.

• Pelvic mass in advanced disease.

• Enlarged uterus.

• Evidence of local tumor extension.

• Signs of metastatic disease in advanced stages.

• Weight loss and general deterioration in advanced disease.

Differential diagnosis

Conditions that may mimic endometrial cancer include:

• Endometrial hyperplasia.

• Endometrial polyps.

• Uterine fibroids.

• Adenomyosis.

• Dysfunctional uterine bleeding.

• Cervical cancer.

• Endocervical polyps.

• Vaginal atrophy.

• Pelvic inflammatory disease.

• Other causes of postmenopausal bleeding.

Diagnostic criteria

Endometrial cancer should be suspected in:

Postmenopausal women

• Any abnormal uterine bleeding occurring after menopause.

Premenopausal women

• Irregular vaginal bleeding.

• Intermenstrual bleeding.

• Persistent abnormal vaginal discharge.

• Dyspareunia.

• Unexplained weight loss.

Definitive diagnosis requires histological confirmation through endometrial biopsy.

Staging

Disease staging should be performed using:

• FIGO staging system.

• TNM staging system.

Investigations

Laboratory investigations

• Full blood count (FBC).

• Liver function tests (LFTs).

• Urea.

• Creatinine.

• Cancer Antigen 125 (CA 125).

Imaging studies

• Chest X-ray (CXR).

• Ultrasound of the abdomen and pelvis.

• Computed tomography (CT) scan of the abdomen and pelvis.

• Magnetic resonance imaging (MRI) of the pelvis.

• Positron emission tomography/computed tomography (PET/CT).

Histopathological investigations

• Endometrial biopsy for confirmation of diagnosis.

Management

Management depends on disease stage, histological subtype, tumor grade, operability, and patient fitness for surgery.

General principles

• Medically operable patients should undergo surgery.

• Surgical specimens should be submitted for histopathological examination and staging.

• Following surgery and receipt of histopathology results, patients should be referred to specialized cancer centers for further management and follow-up.

Non-pharmacological treatment

Surgical management for all operable patients

Perform:

• Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO).

Or

• Radical hysterectomy if there is cervical stromal involvement.

Additional procedures include:

• Peritoneal cytology.

• Selective pelvic and para-aortic lymph node dissection for myometrial invasion or grade 2–3 disease.

Lymph node assessment may include:

• Para-aortic nodes.

• Common iliac nodes.

• External iliac nodes.

• Internal iliac nodes.

• Obturator lymph node chains.

Stage IA and IB

Grade 1 disease

• Observation.

Grade 2–3 disease or presence of adverse features

• Vaginal brachytherapy:

  • 7 Gy × 3 fractions.

Stage IA, IB, and II clear cell or serous carcinoma and Stage IB high-grade disease

One of the following may be offered:

• Adjuvant chemotherapy plus vaginal brachytherapy:

  • 7 Gy × 3 fractions.

Or

• Pelvic external beam radiation therapy:

  • 46 Gy.

Stage III disease

• Adjuvant chemotherapy plus radiotherapy.

High-risk disease:

• External beam radiotherapy (EBRT):

  • 46 Gy.

• Vaginal brachytherapy:

  • 7 Gy × 3 fractions.

Stage IV disease

• Chemotherapy.

Inoperable Stage IIB–IVA disease

• Radiotherapy and/or chemotherapy may be offered as neoadjuvant treatment prior to surgery.

Pharmacological treatment

Cytotoxic therapy for inoperable, metastatic, or recurrent disease is administered with palliative intent.

Regimen 1

Doxorubicin

• 60 mg/m² intravenously over 30 minutes on Day 1.

AND

Cisplatin

• 50 mg/m² intravenously over 1 hour on Day 1.

Repeat every 21 days for 4–6 cycles.

Regimen 2

Cisplatin

• 50 mg/m² intravenously over 1 hour on Day 1.

AND

Doxorubicin

• 45 mg/m² intravenously over 20 minutes on Day 2.

AND

Paclitaxel

• 160 mg/m² intravenously over 3 hours on Day 2.

AND

Filgrastim

• 5 micrograms/kg subcutaneously on Days 3–12.

Repeat every 21 days for 4–6 cycles.

Regimen 3

Carboplatin

• AUC 5–6 intravenously over 1 hour on Day 1.

AND

Paclitaxel

• 175 mg/m² intravenously over 3 hours on Day 1.

Repeat every 21 days for 4–6 cycles.

Management according to underlying cause

Not applicable, as treatment is determined by disease stage, histological subtype, tumor grade, and operability rather than underlying etiology.

Referral

Refer all patients with suspected or confirmed endometrial cancer to a gynecologist for evaluation and surgical management.

Following surgery and histopathological diagnosis:

• Refer all patients to specialized cancer centers for definitive oncological management and follow-up.

Urgent referral is indicated for:

• Histologically confirmed endometrial cancer.

• Advanced-stage disease.

• Suspected metastatic disease.

• Recurrent disease.

• Medically complex cases requiring multidisciplinary management.

Complications

• Local tumor progression.

• Myometrial invasion.

• Cervical involvement.

• Regional lymph node metastasis.

• Distant metastasis.

• Tumor recurrence.

• Treatment-related complications.

• Cancer-related mortality.

Prognosis

Prognosis depends on stage at diagnosis, histological subtype, tumor grade, and response to treatment. Patients diagnosed with early-stage disease generally have favorable outcomes, whereas advanced-stage and high-grade tumors are associated with poorer survival and increased recurrence rates.

Prevention

• Maintenance of healthy body weight.

• Regular physical activity.

• Control of diabetes mellitus.

• Healthy balanced diet with reduced excess fat intake.

• Early evaluation of abnormal uterine bleeding.

• Prompt investigation of postmenopausal bleeding.

• Regular gynecological assessment for women at increased risk.