Uterine Cancer

According to the 2022 statistics data released by Hong Kong Cancer registry, uterine cancer ranked the fourth most common female cancer in Hong Kong, accounting for 6.6% of all new female cancer cases. There were 1,188 new cases of uterine cancer in 2022. On average, one out of 56 females were diagnosed with uterine cancer. The median age at diagnosis was 57.5 years old.

Uterine cancer was the eleventh leading cause of female cancer deaths in Hong Kong. In 2022, it claimed 109 deaths, accounting for 1.7% of all cancer deaths. 

What is uterine cancer?

The uterus is part of the female reproductive system, located in the pelvic region in the lower abdomen. The uterus is connected to left and right ovaries by 2 oviducts, and the lower part of uterus is connected to the cervix and vagina.

It is composed of mainly three layers: the endometrium (inner layer), myometrium (muscular middle layer), and perimetrium (outer layer). The endometrium is composed of numerous capillaries (small blood vessels). Its main function is to provide an appropriate environment for embryo implantation. Female hormones secreted by the ovaries (estrogen & progesterone) are key components towards the normal growth of endometrium. An abnormal secretion is linked with an increased risk in uterine cancer.

Uterine cancer is a cancer growing from the endometrium. In mid to late stage, cancerous cells will spread to structures near the uterus. It may also spread through lymph and bloodstream to other organs like liver and bones.

• Age:
  • > 60 years old, especially those after menopause
• Menstrual periods:
  • Early first period (before 12 years old)
  • Late menopause (after 52 years old)
  • Irregular menstruation
• Not experiencing pregnancy
• Family history:
  • Breast, ovarian or colon cancer before 50 years old in immediate family members (mother, sister or daughter)
• Medical history:
  • Being overweight or obese
  • Breast, ovarian or colon cancer
  • Polycystic ovarian syndrome (PCOS)
  • Endometrial hyperplasia
  • Diabetes mellitus, high triglyceride, high blood pressure and high blood glucose
• Drug history:
  • Estrogen-only hormone replacement therapy (HRT)
  • Tamoxifen (used to treat breast cancer)

Patients with uterine cancer usually presents with abnormal vaginal bleeding. If symptoms are discovered and medical advice is sought immediately, uterine cancer can be diagnosed at an early stage.

• Early stage:
  • Before menopause: irregular bleeding, long and frequent period, excessive amount of bleeding
  • After menopause: sudden bleeding, abnormal discharge from vagina
• Late stage:
  • Lower abdominal pain / distension
  • Pelvic pain during sexual intercourse or urination
  • Abnormal bowel movement (constipation)
  • Blood in vagina
  • Weight loss
  • Shortness of breath

Initial diagnosis:

• Pelvic examination
  • Finger and speculum will be used to observe any abnormalities in the vulva, vagina and cervix.
• Endometrial biopsy
  • A thin tube will be inserted into the uterus to extract a small portion of endometrium, and the histology of the sample will be examined under a microscope to confirm the presence and type of cancer cells. 

• Ultrasound
  • Ultrasound is useful in postmenopausal women whose endometrium should be thin.
  • If the endometrial lining is thicker than normal in postmenopausal women, further tissue evaluation is required.
  • Ultrasound is not as useful in premenopausal women, as the thickness of the endometrium varies during the ovulation / menstrual cycle.
  • Vaginal ultrasound is preferred, where a tubular probe will be inserted in the vagina. When vaginal scan is not feasible, transabdominal ultrasound may be the alternative.

Figure: Transvaginal ultrasound

• Hysteroscopy and biopsy / dilatation and curettage
  • Under local / general anaesthetics, a fibre optic camera will be inserted into the uterus via the vagina. Tissue sampling will be performed, and suspicious tissues will be biopsied. The pathologists will evaluate the cells under microscope to confirm the presence and type of cancer cells.

Further diagnosis:

• Computer Tomography (CT) scan
  • A contrast medium will be injected intravenously, and radiographs will be taken from various angles.  Computers are used to compose a cross-sectional image, and the spread of the cancer will be evaluated.
• Magnetic Resonance Imaging (MRI)
  • A scan of soft tissues near pelvis (lymph nodes, endometrium and myometrium) to evaluate any local spread
• Upper abdominal ultrasound scan
  • To check for any cancer cells that might have metastasized to other organs like liver
• Chest x-ray or CT of thorax
  • To check for any cancer cells that might have metastasized to the lungs or lining of the thoracic cavities
• Blood-taking (tumour marker CA-125)
  • A proportion of uterine cancer cells will secrete a protein tumour marker called CA-125.
  • If it is higher than normal before treatment, it can be used to monitor treatment response and disease progression.
  • CA125 is not specific to uterine cancer and it should only be checked after medical consultation.

According to the International Federation of Gynecology and Obstetrics (FIGO), uterine cancer can be classified into four stages:

• Stage I
  • Cancerous cells are found within endometrium or myometrium.
  • Stage IA: Cancerous cells are within endometrium / less than half of myometrium.
  • Stage IB: Cancerous cells have spread to more than half of myometrium.
• Stage II
  • Cancerous cells have spread from uterus to cervix (metastasis is limited within uterus).
• Stage III
  • Cancerous cells have spread into the pelvic cavity.
  • Stage IIIA: Cancerous cells have metastasised to the covering of the uterus (serosa), oviduct or ovaries.
  • Stage IIIB: Cancerous cells have spread to tissues outside of the uterus (parametria), or vagina.
  • Stage IIIC1: Cancerous cells have spread towards lymph nodes in pelvis.
  • Stage IIIC2: Cancerous cells have metastasised to paraaortic lymph nodes.
• Stage IV
  • Cancerous cells have spread to colon, bladder and distal organs.
  • Stage IVA: Cancerous cells have spread to colon and bladder mucosa.
  • Stage IVB: Cancerous cells have spread to lymph nodes in the inguinal region, and distal organs; e.g. bones and lung.

Grading is a description of cancerous cell differentiation. It is used to predict the magnitude of metastasis.

Unlike normal cells, cancerous cells cannot split normally.  Therefore, pathologists can examine the tissue samples through microscopes to grade them.

• GX: pathologists are unable to determine a grade
• G1: cancerous cells are well-differentiated
• G2: cancerous cells are moderately differentiated
• G3: cancerous cells are poorly differentiated

The current treatment options for localised uterine cancer are surgeries and radiotherapy. The two options can proceed on their own or be done together at the same time. The recovery rates of early staged uterine cancer are above 90%.

Total uterus resection (i.e. Total hysterectomy)

• Preferred option for early-stage cancer
• Procedure: resection of uterus, cervix, oviducts, ovaries, with or without part of the vagina, nearby tissues and lymph nodes. Pathological examination follows in order to determine type of cancer and any metastasis.
• There are 4 methods of resection:
  • Abdominal hysterectomy
  • Vaginal hysterectomy
  • Laparoscopy
  • Robot-assisted
• If the pathological reports confirm a poorly differentiated tumour, or an invasion into myometrium or cervix, then radiotherapy and/or chemotherapy is needed after surgery to minimise risks of cancer recurrence.
• Risk of surgeries include anaesthetic risks, post-surgical infections, bleeding, damage to bladder or intestines (risk ≤ 1-2%) and ureter, healing issues, menopausal symptoms.

Radiotherapy

• May be considered for late-stage uterine cancer patients to control symptoms, and those who cannot proceed with total uterus resection
• Radiotherapy may be considered after surgery in combination with chemotherapy for certain early-stage uterine cancer patients who bear risk factors for local recurrence
• Procedure: high-energy radiation is used to eradicate cancerous cells.

1. External beam radiation therapy (EBRT)

• A linear accelerator is used to shine radiation particles into the tumour and the pelvis to kill the tumour cells.
• For the treatment of uterine cancer, EBRT is typically given 5 days a week for 5-6 weeks.
• During the simulation session for radiotherapy, you will lie on your back and stay very still. We will fit you in a prop to ensure you are in the same position for each treatment. Then, a CT scan will be performed to create detailed images of your pelvis. These images help your doctor plan the treatment, ensuring that the radiation targets the tumour cells precisely while sparing the surrounding healthy tissues.
• Short term adverse effects: appear during treatment / 2-3 weeks after treatment. Possible side effects include skin reddening, fatigue, diarrhoea and pain whilst urination.
• Medium to long term adverse effects: appear few months or even years after treatment. Possible side effects include shortening, narrowing, dryness, pain or secretion in the vagina. Other low risk but potentially serious complications include intestinal adhesions, inflammatory bowel disease, inflammation of the bladder and overactive bladder.

2. Brachytherapy (internal radiotherapy)

• For post-operative uterine cancer patients, brachytherapy (internal radiotherapy) involves placing a radiation-emitting tube inside your vagina under local anesthesia. This method delivers high doses of radiation to the former tumor site while sparing healthy tissues. 
• It can be performed alone after surgery or following external beam radiation therapy (EBRT).
• Adverse effects:
  • Radiation may affect vagina, bladder and colon.
  • Possible side effects include shortening, narrowing, dryness, pain or secretion in the vagina. Other less common but potentially serious complications include intestinal adhesions, inflammatory bowel disease, inflammation of the bladder and overactive bladder.

Chemotherapy

• Chemotherapy is used for patients at high risk of recurrence. It can be administered after surgery, with or without radiotherapy, in early-stage uterine cancer to reduce local recurrence risk. 
• In advanced or recurrent uterine cancer, chemotherapy reduces tumor size, slows growth, and relieves symptoms. It may be combined with immunotherapy or targeted therapy for selected patients.
• Two common chemotherapy combinations are:
  • Carboplatin and paclitaxel 
  • Cisplatin and doxorubicin.
• Adverse effects:
  • Seen whilst treatment but symptoms will diminish afterwards.
  • Possible side effects include fatigue, decreased immunity, nausea, decreased appetite and alopecia.
  • Doxorubicin: the heart may be affected
  • Cisplatin: the kidneys may be affected
  • Paclitaxel: the nerves may be affected; limbs may experience tingling sensations and numbness.

Immunotherapy

• Immune checkpoint inhibitors are immunotherapy drugs that help the body fight cancer by targeting proteins on immune and cancer cells. These proteins, called checkpoints, can prevent the immune system from attacking cancer cells. PD-1 on T cells binds to PD-L1 on cancer cells, sending an inhibitory signal to stop the attack. Drugs like pembrolizumab (Keytruda) and nivolumab (Opdivo) block this interaction, enabling T cells to destroy cancer cells.
• Possible side effects: feeling tired or weak, fever, cough, nausea, itching and skin rash, loss of appetite, muscle or joint pain, shortness of breath, constipation or diarrhoea
• Less common but more serious side effects: infusion reactions (fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing), autoimmune reactions (serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidney, skin, or other organs)

Pembrolizumab

• Pembrolizumab can be used for advanced uterine cancer:
  • Combined with carboplatin and paclitaxel, then solo pembrolizumab, for adult patients with primary advanced or recurrent endometrial carcinoma.
  • For patients with high microsatellite instability (MSI-H).
  • For those with mismatch repair gene defects (dMMR).
  • Effective in cases with high tumor mutational burden (TMB-H).
  • Combined with lenvatinib for advanced uterine cancer without dMMR.
• Administration: Intravenous (IV) infusion once every 3 to 6 weeks

Dostarlimab

• Dostarlimab for advanced uterine cancer:
  • First-line: Combined with carboplatin and paclitaxel, followed by maintenance dostarlimab, for dMMR or MSI-H cancer cells.
  • Second-line: Alone after chemotherapy for dMMR cancer cells
• Administration: Intravenous (IV) infusion, once every 3 weeks at first, and then every 6 weeks

Targeted therapy

• Targeted therapy might be used alone or in combination with other treatments in selected patients with advanced uterine cancer.

Hormonal therapy

• Hormonal therapy, sometimes combined with chemotherapy, can be used for advanced or recurrent uterine cancer. It is typically applied to lower grade endometrioid histologies, preferably in patients with small volume disease or slow-growing tumors.
• Types of hormonal therapy: 
  • Progestins (lab-made versions of the hormone progesterone) e.g. medroxyprogesterone (Provera), megestrol, levonorgestrel released from an intrauterine device (IUD)
  • Tamoxifen (Nolvadex)
  • Luteinising hormone-releasing hormone (LHRH) or gonadotropinreleasing hormone (GnRH) agonists e.g. goserelin (Zoladex), leuprorelin (Enantone)
  • Aromatase inhibitors e.g. letrozole (Femara), anastrozole (Arimidex), exemestane (Aromasin)
  • Fulvestrant (Faslodex)
• Side effects: hot flashes, night sweats, weight gain, worsening of depression, increased blood sugar levels in women with diabetes, vaginal dryness, joint and muscle aches, osteoporosis, rare but serious blood clots

• Giving birth
  • Among those who have given birth, female hormones have a protective effect on the endometrium.  Therefore, risks for uterine cancer are lowered.
• Lactation
  • During lactation, female hormones will decrease. Uterus will be less affected and results in a lower risk for uterine cancer.
  • Longer lactation period can reduce the risk of uterine cancer.
• Regular menstruation
  • As a result of long menstrual intervals without regular shedding of the endometrium, the endometrial cells will be thickened and risks for hyperplasia and uterine cancer will be increased.
  • It is essential to use hormones, such as combined oral contraceptive pills or progestogen-only pills, to help to shed the endometrium and induce withdrawal bleeding every 2-3 months.
  • Oral progestogen or progestogen-releasing intrauterine conceptive device may also be considered for patients with heavy menstruation or endometrial hyperplasia.
• Diet
  • Having a healthy diet can reduce risk for uterine cancer.
  • More high-fibre food should be consumed.
  • Reduce consumption of high-fat, high-sodium and high-sugar food.
  • Consume less red meat (beef, pork), manufactured food, pickled food and alcohol.
• Prophylactic removal of uterus +/- ovaries for Lynch syndrome carriers
• Others
  • Regular exercises
  • Weight control
  • Good control of diabetes and mellitus, hypertension, and hyperlipidemia

American Cancer Society: Endometrial Cancer

Cancer Council: Uterine cancer

Hong Kong Cancer Registry: Overview of Hong Kong Cancer Statistics of 2022

Hospital Authority Smart Patient: Corpus Cancer

Macmillan Cancer Support: Womb Cancer

NCCN Guidelines. Uterine Neoplasms. Version 1.2025

NCCN Guidelines for Patients. Uterine Cancer, 2023 

Special thanks to Mr. Jerome Cheuk-Him Lee (Class M25), Ms. Katrina Tung-Yee Tse (Class M25), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Ka-Yu Tse, Department of Obstetrics & Gynaecology, the University of Hong Kong for authoring and editing this article.

Last updated on 15th Jan, 2025.