Endometrial cancer arises from the lining of the uterine body (corpus). It is the most common gynecologic cancer in high-income countries, usually occurs after menopause (peak in the 60s), and is often found early because it causes abnormal bleeding. Incidence is rising with obesity.

Two broad groups

Molecular classification (POLE-mutated, mismatch-repair deficient, p53-abnormal, no specific molecular profile) now refines prognosis and treatment. All endometrial cancers are tested for mismatch-repair deficiency, which also screens for Lynch syndrome.

Risk factors — anything that increases estrogen exposure without progesterone

• Obesity (adipose tissue converts androgens to estrogen) — the strongest modifiable factor
• Chronic anovulation: PCOS, anovulatory infertility
• Estrogen-alone hormone therapy in a woman with a uterus
• Tamoxifen (estrogen-like effect on the endometrium)
• Diabetes and insulin resistance, hypertension
• Nulliparity, early menarche, late menopause
• Estrogen-secreting ovarian tumors (granulosa cell tumor)
• Lynch syndrome (hereditary nonpolyposis colorectal cancer) — lifetime risk up to about 40–60%
• Increasing age

Protective: combined oral contraceptives, levonorgestrel IUD, parity, breastfeeding, physical activity, weight control.

• Abnormal uterine bleeding is the cardinal symptom (about 90%)
  • Postmenopausal bleeding — any spotting, staining, or bleeding after menopause
  • Before menopause: heavy, prolonged, or intermenstrual bleeding, especially at 45 or older or with obesity/PCOS
• Watery or blood-tinged discharge; pyometra in older women
• Late: pelvic pain or pressure, enlarged uterus, abdominal distension, weight loss, leg swelling, cough (metastases)
• History: onset, pattern, and amount of bleeding; hormone use (estrogen alone, tamoxifen); obesity, diabetes, PCOS; family history of colorectal, endometrial, or ovarian cancer (Lynch syndrome)

• Endometrial biopsy (office sampling) — the standard first diagnostic test; histology confirms the diagnosis
• Transvaginal ultrasound — in postmenopausal bleeding, a thin endometrium (≤ 4 mm) makes cancer unlikely; a thicker or poorly seen lining requires sampling. Persistent bleeding needs sampling even when the lining is thin
• Hysteroscopy with directed biopsy or dilation and curettage (D&C) when office biopsy is nondiagnostic or not possible
• Pap test is not a diagnostic test for endometrial cancer (it rarely detects it)
• Staging workup: CBC, chemistry, chest imaging; CT or MRI for extent; CA-125 may be raised in advanced or serous disease
• No routine screening for average-risk women — teach them to report bleeding. For Lynch syndrome carriers, endometrial sampling may be offered every 1–2 years starting at 30–35, with risk-reducing hysterectomy and bilateral salpingo-oophorectomy after childbearing (around 40)

Surgical staging (FIGO 2023, simplified)

• Stage I: confined to the uterine corpus — IA invasion of less than half the myometrium, IB half or more (non-aggressive types)
• Stage II: invasion of the cervical stroma (or aggressive histology with myometrial invasion)
• Stage III: spread to serosa, adnexa, vagina, parametria, or pelvic/para-aortic nodes
• Stage IV: bladder or bowel mucosa, or distant spread
• Depth of myometrial invasion, histologic type and grade, lymphovascular invasion, and molecular class determine risk and adjuvant therapy

Surgery — primary treatment for most

• Total hysterectomy with bilateral salpingo-oophorectomy (BSO) plus lymph node assessment (sentinel lymph node mapping) — a minimally invasive (laparoscopic or robotic) approach is preferred when feasible (faster recovery, fewer wound complications, same survival)
• Omentectomy and peritoneal biopsies are added for serous and other aggressive types (they behave like ovarian cancer)
• Radical hysterectomy is not standard for endometrial cancer (it is used for cervical cancer)

Adjuvant therapy (based on risk)

• Stage IA low-grade endometrioid: surgery alone is usually enough
• Intermediate risk (deep invasion, high grade, lymphovascular invasion, older age): vaginal brachytherapy (reduces vaginal-cuff recurrence) or pelvic external beam radiation
• Advanced or high-risk: chemotherapy (carboplatin and paclitaxel), often with immunotherapy (dostarlimab or pembrolizumab), with or without radiation

Hormonal therapy

• High-dose progestins (megestrol acetate, medroxyprogesterone acetate, levonorgestrel IUD) — activate progesterone receptors, oppose estrogen, and cause endometrial differentiation and atrophy
  • Used for fertility-sparing treatment of selected young women with grade 1 endometrioid cancer limited to the endometrium (with repeated sampling every 3–6 months), and for advanced or recurrent hormone-receptor-positive disease
  • Adverse effects: weight gain, fluid retention, VTE, hyperglycemia, mood change — contraindicated with active thromboembolism
• Other options for recurrence: tamoxifen alternating with a progestin, aromatase inhibitors
  • Tamoxifen: VTE, stroke, endometrial stimulation (report bleeding), hot flashes; teratogenic; strong CYP2D6 inhibitors (paroxetine, fluoxetine) reduce its effect
  • Aromatase inhibitors: bone loss (DXA, calcium and vitamin D), joint pain, hot flashes

Drug safety (consistent with cancer treatment and breast disorders)

• Carboplatin: myelosuppression (especially thrombocytopenia), hypersensitivity that becomes more likely after many cycles — stop the infusion immediately with any reaction
• Paclitaxel: hypersensitivity (premedicate with a corticosteroid and antihistamines), peripheral neuropathy, alopecia, neutropenia
• Immune checkpoint inhibitors: immune-related colitis, pneumonitis, hepatitis, endocrine disorders (thyroid, adrenal, pituitary, new diabetes) — may appear weeks to months later
• Cisplatin (used in some regimens): nephrotoxicity, ototoxicity
• All cytotoxic drugs are teratogenic; use hazardous-drug precautions

Listed in priority order.

1. Hypersensitivity/anaphylaxis during chemotherapy infusion (dyspnea, urticaria, wheezing, hypotension, flushing, back pain): stop the infusion immediately, keep the IV line open with normal saline, stay with the client, call for help, assess airway, breathing, and circulation, give epinephrine IM for anaphylaxis and other emergency drugs per protocol
2. Postoperative bleeding and hemodynamics — vital signs, dressing and vaginal bleeding, hemoglobin, urine output
3. Detect urinary tract injury — large amounts of clear, watery fluid from a drain or the vagina may be urine (ureteral or bladder injury): report promptly; flank pain, decreasing urine output, or rising creatinine are also warning signs
4. VTE prevention — pelvic cancer surgery is high risk: early ambulation, sequential compression devices, anticoagulant prophylaxis (often extended for about 4 weeks after cancer surgery), leg exercises
5. Respiratory care and pain — incentive spirometry, splinting, multimodal analgesia
6. Bowel and bladder — monitor for ileus; avoid straining (stool softeners)
7. Chemotherapy and radiation side effects — neutropenia precautions, mucositis care (soft toothbrush, bland rinses), nausea (scheduled antiemetics), radiation cystitis (fluids, avoid caffeine, alcohol, spicy foods), diarrhea
8. Psychosocial and sexual health — surgical menopause, loss of fertility, body image. Use therapeutic communication that clarifies the concern (e.g., "Are you worried about how surgery may affect your sexual life?") rather than false reassurance

• Any bleeding after menopause must be reported — early evaluation is the main reason endometrial cancer is usually curable
• Risk reduction: weight management, physical activity, diabetes control; with an intact uterus, estrogen therapy must include a progestogen; women on tamoxifen report vaginal bleeding
• After hysterectomy
  • No heavy lifting (more than about 4.5 kg / 10 lb) or strenuous exercise for about 4–6 weeks (open surgery may need longer)
  • No intercourse, tampons, or douching until the provider confirms the vaginal cuff has healed (usually about 6–8 weeks)
  • Showers are allowed; avoid tub baths and swimming until incisions and the vaginal cuff heal
  • Prevent constipation (fluids, fiber, stool softeners) — straining increases pressure on the surgical site
  • Report fever, foul-smelling discharge, heavy vaginal bleeding, calf pain or swelling, dyspnea, burning on urination, or leakage of urine from the vagina
  • Surgical menopause after BSO: hot flashes and vaginal dryness may appear — discuss options with the oncology team
• Chemotherapy: fever of 38.0 °C (100.4 °F) or higher — call immediately; soft toothbrush for mouth sores; avoid crowds and sick contacts during low counts; take antiemetics on schedule; hair loss is usually temporary; tingling or numbness in hands and feet should be reported
• Radiation: drink plenty of fluids; avoid bladder irritants; use vaginal dilators as instructed after vaginal brachytherapy to prevent stenosis
• Genetic counseling if Lynch syndrome is found — relatives need colorectal and gynecologic surveillance
• Follow-up: visits every 3–6 months for the first 2–3 years; report new bleeding, pelvic pain, cough, or weight loss

• Postmenopausal bleeding is the cardinal sign — always evaluate
• Main cause: unopposed estrogen — obesity, PCOS/anovulation, estrogen-alone therapy, tamoxifen, nulliparity, early menarche/late menopause
• Parity and combined oral contraceptives are protective
• Diagnosis: endometrial biopsy; TVUS endometrium ≤ 4 mm makes cancer unlikely; Pap test does not diagnose it
• Lynch syndrome: test all tumors for mismatch-repair deficiency
• Standard surgery: total hysterectomy + BSO + sentinel node assessment, minimally invasive preferred
• Stage I vs. II = cervical stromal invasion; IA vs. IB = myometrial invasion depth (less than or at least half)
• Low-risk stage IA low grade: surgery alone; intermediate risk: vaginal brachytherapy
• Hormonal treatment = high-dose progestins (weight gain, fluid retention, VTE)
• Chemotherapy reaction: stop the infusion first, keep the line open with saline
• Clear watery drainage after hysterectomy → suspect urinary tract injury
• After hysterectomy: no intercourse until cleared (about 6–8 weeks); avoid straining and heavy lifting