Uterine (Endometrial) Cancer Diagnosis & Treatment in Singapore
What type of Uterine Cancer Treatment Will I Need?
Treatment options and recommendations depend on several factors, including the stage of cancer, the subtype of endometrial cancer, treatment side effects, patient’s overall health and personal preferences.
Endometrial (uterine) cancer is treated by one or a combination of treatments, which include:
- Surgery
- Radiation therapy
- Anti-cancer drug therapy
Surgery
Endometrial cancer surgery has two purposes:
- To remove the cancer
- To stage the cancer
Surgery involves the removal of the uterus (hysterectomy), the ovaries and the fallopian tubes (salpingo-oophorectomy). The surgeon may also remove the lymph nodes around the tumour. The tissues removed during surgery are checked under a microscope for cancer cells. This helps to determine if cancer has spread outside the uterus and the extent of cancer spread, which is also known as cancer staging.
The surgery may be performed either by abdominal incision (known as laparotomy) or by key-hole surgery (laparoscopy) which uses several small incisions.
If I have endometrial cancer, can I still get pregnant?
Hysterectomy (removal of the uterus) is a very effective treatment for early endometrial cancer. However, after a hysterectomy, a woman can no longer become pregnant. Fertility preservation treatment using progesterone may be possible for certain women with early endometrial cancer. Premenopausal women who desire to preserve their fertility can discuss with their oncologist if they are suitable for fertility preservation procedure.
Radiation Therapy
Radiation uses high-energy X-rays to kill cancer cells.
Radiation may be used after surgery to prevent uterine cancer from coming back to the pelvis. Radiation treatment may include:
- External beam radiation therapy: a machine outside the body directing radiation towards the pelvis to treat cancer cells in this region.
- Internal radiation therapy: radiation source sealed in catheters, needles, wires placed inside the vagina. This enables radiation to be delivered directly to the lower pelvic area.
For advanced cancers (cancer that has spread), radiotherapy can help relieve localised problems caused by the cancer, such as relieving bone pain caused by cancer in the bone.
Drug Therapy
Unlike surgery and radiation therapy which target cancer in specific areas of our body, drug therapy enters our bloodstream, travels throughout the body and can reach and kill cancer cells that have spread to parts of the body far away from the original cancer.
Historically, chemotherapy is the most common drug therapy used in the treatment of endometrial cancer. In recent years, oncologists have made significant strides in treating endometrial cancer. Newer non-chemotherapy drug treatments, such as targeted therapy and immunotherapy, have been added to the treatment armamentarium. Every endometrial cancer is unique. A better understanding of the mechanisms that drive individual cancer growth enables oncologists to target cancer growth more precisely using targeted therapy. Immunotherapy is an exciting new treatment that has revolutionized the way we treat endometrial cancer.
The main types of drug therapy used in endometrial (uterine) cancer treatments are:
- Chemotherapy
- Hormones
- Targeted Therapy
- Immunotherapy
Chemotherapy
Chemotherapy is a drug treatment that kills cancer cells. It works by targeting fast-growing cells in our body. Because cancer cells usually grow faster than normal cells, chemotherapy causes more damage to the cancer cells, but may also cause collateral damage to the fast-growing healthy cells in our body. These include our hair follicles, the cells lining our digestive tract and our immune cells, causing hair loss, nausea and vomiting and a weakened immune system.
A number of chemotherapy drugs are used in treating endometrial (uterine) cancer. The commonly used drugs include carboplatin, cisplatin, paclitaxel, doxorubicin and pegylated liposomal doxorubicin. These drugs can be used on their own, or more commonly, in combination.
Side effects of chemotherapy are drug dependent and also patient dependent. In recent years, major advancements have been made in the prevention and amelioration of chemotherapy side effects, especially in the prevention of nausea, vomiting and infections. Hair loss caused by chemotherapy may be minimised with scalp cooling. Your uterine cancer specialist in Singapore will provide you with an in-depth discussion of the relevant side effects so you can better understand them.
Hormones
Some endometrial cancers contain estrogen and/or progesterone receptors. An excessive amount of the female hormone estrogen, or insufficient progesterone hormone in our body, can promote cancer growth in this type of cancer. Hormone therapy can slow down or stop the growth of these hormone-dependent cancers by either increasing the progesterone or reducing the estrogen levels.
Hormone therapy used in the treatment of endometrial (uterine) cancer includes:
- Progestogen is a synthetic form of progesterone. It is the most common hormone therapy used in treating endometrial cancers.
- Aromatase inhibitor (such as letrozole and anastrozole) blocks estrogen.
- Tamoxifen is an anti-estrogen drug. When used in the treatment of endometrial cancer, tamoxifen is alternated with progestogen.
Side effects of hormonal therapy are generally mild.
Side effects of progestogen therapy may include fluid retention, increase in appetite and weight gain. An uncommon but serious side effect includes blood clots in the legs or the lungs.
Aromatase inhibitors may cause menopausal symptoms such as hot flushes, body aches and also bone-thinning.
Tamoxifen may cause menopausal symptoms. Less common but serious side effect includes blood clot in the legs or the lungs.
Your oncologist will provide you with an in-depth discussion of the relevant side effects so you can better understand them.
Targeted therapy
Every endometrial cancer is unique. Each and every tumour has a unique set of genes, proteins or other substances that drives cancer growth. This is also known as a tumour’s molecular profile.
Targeted therapy is a cancer treatment that uses drugs designed to block or target specific genes and proteins involved in the growth and survival of cancer cells. They are sometimes called “molecularly targeted drugs”, “designer drugs” or “precision medicines”. Targeted therapy can be used on its own, or together with other cancer treatments such as chemotherapy.
Types of targeted therapy used in endometrial (uterine) cancer treatments include:
- Anti-angiogenic
- Anti-HER 2
- Anti-NTRK
How to Identify targets for targeted therapy?
Tests can be performed on a sample of your tumour taken during surgery or biopsy to determine the molecular profile of your tumour. In particular, information on the mismatch repair genes, the HER2 and the hormonal status can help your oncologist select the most appropriate targeted therapy for your endometrial cancer.
Anti-angiogenic:
Cancer relies on blood vessels to deliver nutrients to enable it to grow, a process called angiogenesis. Anti-angiogenic drugs block the formation of blood vessels, thereby resulting in the death of cancer cells through “starvation”.
Anti-angiogenic drugs used in treating endometrial cancer include:
- Lenvatinib which is an oral drug (taken by mouth). This drug is often given together with immunotherapy when used in the treatment of endometrial cancer.
- Bevacizumab is usually combined with chemotherapy when used in the treatment of endometrial cancer
Anti-HER2:
Uterine serous carcinoma is a rare but aggressive type of endometrial cancer. About 25% of these cancers produce a rogue protein, HER2, which contributes to its aggressiveness. Anti-HER2 therapy, such as trastuzumab, a drug commonly used in treating HER2-containing breast cancer, can be used in the treatment of this subtype of endometrial cancer.
Anti-NTRK:
Very rarely, endometrial cancer may contain NTRK fusion proteins, which are abnormal proteins that can promote cancer growth. Anti-NTRK drugs, such as entrectinib and larotrectinib, block the NTRK fusions proteins and can be quite effective in slowing down the growth of such cancers.
Side effects of targeted therapy dependent on the type of targeted drugs used and also the patient. The side effects of targeted therapy differ from those of chemotherapy. As this class of drug targets mainly the cancer cells, they are therefore less likely to cause collateral damage to our normal healthy cells. Unlike chemotherapy, targeted therapy does not usually cause hair loss or serious infections. Your oncologist will provide you with an in-depth discussion of the relevant side effects so you can better understand them.
Immunotherapy
Immunotherapy is a drug therapy that harnesses the natural defences of our own immune system to fight cancers. However, cancer can find ways to escape detection by our immune system. For example, it can produce a protein called the PD-L1, which “switches-off” our immune system and prevents it from attacking the cancer.
Immunotherapy drug, such as pembrolizumab, blocks the effect of PD-L1 proteins on our immune system. This switches our immune system back to the “on” mode to attack the cancer. This type of immunotherapy is also known as immune checkpoint inhibitor.
Immunotherapy is an exciting new treatment that has revolutionized the way we treat endometrial cancer; cancer control can be quite dramatic and, in some women, long-lasting cancer control may be achieved.
Immunotherapy is currently indicated in women with advanced endometrial cancer or in women whose endometrial cancer has come back (recurrent cancer). It is most effective in the subtype of endometrial cancer with mismatch repair gene defects. When cells in our body divide and multiply, DNA errors (mutations) can occur, which are fixed by the mismatch repair genes. Cancers with defective (mutated) mismatch repair genes accumulate large quantities of DNA mutations. The more DNA mutations a cancer cell has, the higher the likelihood it will be recognized by the immune system as foreign and get killed.
Endometrial cancer with mismatch repair gene defects:
Approximately 25 to 30 % of endometrial cancer have mismatch repair genes that are defective. This includes endometrial cancer associated with Lynch syndrome, a hereditary condition where a mutated mismatch repair gene is inherited from the parent. Immunotherapy is highly effective in this subtype of endometrial cancer. Cancers with mismatch repair gene defects are also called “MSI-high” or “microsatellite-instable” cancers.
Endometrial cancer without mismatch repair gene defects:
Endometrial cancers without mismatch repair defects are less likely to respond when treated with immunotherapy alone. Adding an anti-angiogenic drug to immunotherapy, such as adding lenvatinib to pembrolizumab, has been shown to be more effective than treatment with immunotherapy alone in this subtype of endometrial cancer. Cancers without mismatch repair gene defects are also called “microsatellite-stable” or “MSS” cancers.
Side effects of immunotherapy may include flu-like symptoms, skin rashes, and inflammation due to an “over-active” immune system. The side effects are generally mild and manageable though in some patients, severe inflammation may occur. Your oncologist will provide you with an in-depth discussion of the relevant side effects so you can better understand them.
Ongoing Research: Doctors are looking for ways to make immunotherapy work better in endometrial cancer. Clinical trials combining immunotherapy with other drugs, such as targeted therapy and /or chemotherapy, are underway.
Treatments for Uterine Cancer (Based on Cancer Stages)
Stage 1 and 2 Endometrial cancer:
Surgery is the mainstay treatment for women with stage I and II endometrial cancer.
Even if your surgery was successful at removing all visible cancers, tiny cancers sometimes remain in the body that we are not able to detect with current tests. After surgery, based on the characteristics of your tumour, your oncologist will advise if further additional treatments in the form of radiation therapy and/or, chemotherapy, are needed to lessen the chance of your cancer coming back.
The good news is that up to 90% of stage I endometrial patients can be successfully treated with surgery alone.
Ongoing Research: Clinical trials are underway to find out if cancer molecular profiling can be used to predict the risk of cancer coming back and the need for further treatment after surgery.
Stage 3 Endometrial cancer:
Surgery is the mainstay treatment. Following surgery, chemotherapy, most commonly a combination of carboplatin and paclitaxel chemotherapy, and radiation therapy is recommended to lessen the chance of cancer coming back.
Stage 4A and 4B Endometrial cancer:
Stage 4A endometrial cancer has grown into the bladder and/or rectum. These cancers are treated with a combination of surgery, chemotherapy and radiation. Your oncologist may recommend chemotherapy to shrink down the cancer before surgery to make them easier to remove during surgery.
Stage 4B endometrial cancer has spread beyond the pelvis to affect distant organs, for example, the lungs, liver, abdominal lining and/or bones.
For most women with stage IVB endometrial cancer, the mainstay treatment is drug therapy and may comprise chemotherapy, hormone, targeted therapy and /or immunotherapy. The choice of drug therapy depends on various factors. Increasingly, the “molecular signature” of individual cancer, such as mismatch repair gene, HER2 and the hormonal status, helps oncologists tailor a treatment that is best suited to an individual .Other factors that influenced drug choice include the side effects of treatment, the overall health and personal preferences of the patient.
For stage IVB endometrial cancer where the cancer spread is still confined to the abdominal cavity, surgery to remove the cancer, also known as debulking surgery, may be considered. Further drug treatment is usually needed after surgery to control the cancer better.
Surgery and radiotherapy are mainly reserved for localised problems caused by the cancer, for example, surgical removal of the uterus when there is severe bleeding from uterine cancer and the use of radiotherapy to relieve bone pain caused by cancer in the bone.
Recurrent endometrial cancers:
Recurrent endometrial cancers are previously treated endometrial cancers that have come back. These cancers are treated the same way as stage IVB endometrial cancer.
Oncologists at OncoCare with Clinical Interests in Uterine Cancers
Cancer is a disease that affects many people and their loved ones. Early detection can thus significantly improve prognosis and increase the likelihood of successful treatment. If you are experiencing any symptoms that could be indicative of cancer, it is important to see an oncologist in Singapore as soon as possible. The right oncologist will work closely with other uterine cancer specialists to provide timely care.
OncoCare’s team of oncologists focuses on diagnosing, screening and treating uterine cancer, breast cancer, lung cancer, colon cancer, hepatobiliary cancer and gynecologic cancer with a sense of urgency.
What is Uterine Cancer?
Uterine cancer is a type of cancer that begins in the womb (uterus). The uterus is the organ where an unborn baby develops and grows when a woman is pregnant.
There are 2 main types of uterine cancer:
- Endometrial cancer
- Uterine sarcoma
Endometrial cancer:
Uterine cancer can begin in the inner lining of the uterus, also known as the endometrium. These cancers are therefore also commonly known as endometrial cancer. This is the most common type of uterine cancer.
Uterine sarcoma:
Uterine cancer can also begin in the muscle layer of the uterus. This type of uterine cancer is also known as uterine sarcoma. This is an uncommon type of uterine cancer.
Endometrial cancer and uterine sarcoma are distinctly different cancers and require different types of treatment.
Endometrial (Uterine) cancer: An Overview
Endometrial (uterine) cancer incidence is on the rise worldwide. There is a strong link between endometrial cancer and “urbanised lifestyle” where women are having fewer children, breastfeed less, and are more likely to be obese and have diabetes.
The good news is that endometrial cancer is often discovered at an early stage because it frequently produces vaginal bleeding. With appropriate treatment, 90% of early endometrial cancer can be successfully treated. Significant progress has been made in the treatment of advanced cancers using newer treatments such as immunotherapy and targeted therapy.
Symptoms and Signs:
What are the warning symptoms and signs of Endometrial (Uterine) cancer?
- Abnormal vagina bleeding or discharge:
Abnormal vagina bleeding or discharge is the most common and an early presenting symptom of endometrial cancer. Any abnormal vagina bleeding or discharge needs to be looked into by your doctor, especially when it happens after menopause.
Other symptoms or signs may include:
- Pressure or pain in the back or pelvis
- Pain during sexual intercourse
- Difficulty or painful urination
- Blood in urine
- Difficulty passing motion
- Blood in stools
Please consult a uterine cancer specialist in Singapore if you experience any of the above persistent signs or symptoms that worry you.
Endometrial (Uterine) cancer: Who is At Risk?
In Singapore, the majority of uterine cancer is diagnosed after 40 years of age, most commonly between 50 and 70 years old. Obesity is a major risk factor for endometrial cancer.
- Hormonal factors
Hormonal imbalance is a key risk factor in endometrial cancer. A balance of the two female hormones, estrogen and progesterone, is what keeps the uterus healthy. Having too much estrogen, or not enough progesterone, increases a woman’s risk of developing endometrial cancer.
Hormonal imbalance can be caused by:
- Obesity
Obesity is a strong risk factor for endometrial cancer. Our body fat can produce estrogen. Obese women are four times more likely to get endometrial cancer.
- Early menarche (before 12 yo) and late menopause (after 50 yo)
- Polycystic ovary syndrome
- Medications that increase Estrogen:
- Tamoxifen
- Estrogen-containing hormone replacement therapy (without progesterone)
- Having colon, ovary or breast cancer in the past
- Close relatives with endometrial or colon cancer
- Diabetes
- Endometrial Hyperplasia: abnormal thickening of the endometrium lining, which can progress to uterine cancer if left untreated.
Is my endometrial cancer hereditary?
3 out of 100 endometrial cancers are hereditary in nature, due to Lynch Syndrome.
We can inherit a damaged or faulty (mutated) gene from either of our parent which puts us at increased risk of endometrial cancer. The genes responsible are called mismatch repair genes. These genes correct the mistakes that occur when our cells copy the DNA when they divide. Mismatch repair gene mutation, therefore, leads to multiple DNA mutations, which can damage our healthy cells and lead to a higher risk of cancer development.
People with Lynch syndrome have an increased risk of developing endometrial and colon cancer. They are also at risk of cancers of the ovary, gastrointestinal tract (stomach, pancreas, liver) and urinary tract.
Why is it important to know if my endometrial cancer is hereditary?
Family members are also at risk of carrying the Lynch syndrome gene and may also need to go for genetic testing.
A personalized plan, which may involve enhanced cancer screening to detect pre-cancer or early cancer, cancer preventative medication or surgery can help to help save lives in people with Lynch syndrome.
Knowing if one’s endometrial cancer is Lynch syndrome associated may impact how we treat the cancer, as these cancers respond exceptionally well to immunotherapy treatment due to their faulty mismatch repair genes.
When do we suspect Lynch syndrome?
Oncology specialists in Singapore may suspect Lynch syndrome when there are multiple family members with cancers linked to Lynch syndrome, especially if these cancers occur at a young age (before the age of 50). Family history on its own, however, is not reliable as a person with Lynch syndrome may not necessarily have a strong history of uterine cancer in the family.
How to test for Lynch syndrome?
- Screening for Lynch syndrome
Doctors can screen for Lynch syndrome using the endometrial cancer tissue that is removed during the surgery to check for mutation in the Lynch Syndrome genes. This screening is increasingly done in women with endometrial cancer even in the absence of suggestive family history.
- Genetic Testing for Lynch syndrome
To confirm the diagnosis of Lynch Syndrome, we need genetic testing. This involves a blood test (or saliva) to check for mutations in the Lynch Syndrome genes.
Before embarking on genetic testing, we recommend that you speak to a uterine cancer specialist in Singapore as they will be able to assess your risk and advise if genetic testing is right for you. This will also ensure that the correct tests are ordered and the results are interpreted correctly.
Diagnosis: How does the doctor know I have Endometrial (Uterine) cancer?
If your doctor suspects endometrial (uterine) cancer, he or she may perform the following tests or treatments:
- Physical examination to check for signs of disease, such as abnormal lumps.
- Ultrasound scan to check for abnormal uterine thickening or masses
- To confirm the diagnosis, a sample of the uterine tissue needs to be removed (biopsy) and sent to the laboratory and checked under a microscope for cancer cells. This can be performed with the following procedure:
- Endometrial biopsy: A thin, flexible tube is introduced into the uterus through the cervix. A small amount of uterine tissue is scraped and removed for testing.
- Dilation and curettage (D&C): A dilator is used to widen the cervix. A curette is introduced through the cervix into the uterus to remove the abnormal tissues in the uterus.
- Hysteroscopy: A thin tube scope is inserted into the uterus via the cervix. This allows the doctor to have a direct view of the uterus. Abnormal looking tissues can be removed and sent for testing.
Of note, PAP smear test screens for cervix cancer by removing cells from the cervix. It is therefore not an effective or reliable test for picking up endometrial cancer located in the uterus away from the cervix.
Types of Endometrial (Uterine) Cancer:
Endometrial cancers can be divided into different subtypes based on histologic features, and more recently, according to their molecular characteristics.
Histologic subtypes:
Historically, endometrial carcinomas can be divided into different types based on their appearance under the microscope, also known as histologic subtypes. They can be broadly divided into endometrioid and non-endometrioid types, and include:
- Endometrioid adenocarcinoma
- Non-endometrioid adenocarcinoma includes:
- Carcinosarcoma (also known as MMMT)
- Serous adenocarcinoma
- Clear Cell adenocarcinoma
- Undifferentiated carcinoma
- De-differentiated carcinoma
Endometrioid adenocarcinoma is the most common type of endometrial cancer. Non-endometrioid adenocarcinomas are less common but are more aggressive and more likely to have spread outside the uterus by the time they are diagnosed.
Molecular subtypes:
In recent years, oncologists have come to realise that endometrial cancer is not a single disease but diverse diseases. No two endometrial cancers are the same.
What is Molecular Profiling (Biomarker profiling)?
Each person’s endometrial cancer has a unique set of genes, proteins or other substances that can provide information about the behaviour of the cancer. For example, endometrial cancer that contains:
- POLE gene mutation (defect) has a good outcome
- p53 mutation are aggressive
- Mismatch repair gene defect (mutation) has intermediate outcome
Importantly, molecular profiling can also help your oncologist pick a cancer treatment that is specially tailored for your cancer as some cancer treatment, including targeted therapies and immunotherapies, may only work for cancers that have a certain molecular profile. Molecular profiling is also known as “biomarker profiling”.
How is Molecular Profiling (Biomarker Testing) test done?
Testing for molecular profile requires a sample of your tumour taken during surgery or biopsy. If you do not have a tumour sample available for testing, for example when there is insufficient tumour material for testing or if the tumour is located in places that are difficult to biopsy, your oncologist may then suggest a liquid biopsy test (blood test).
Endometrial (Uterine) Cancer Staging: Has my cancer spread?
After endometrial cancer has been diagnosed, tests are done to find out if cancer is still confined to the uterus, or if it has spread to other parts of the body. The stage of the cancer affects the long-term outlook and how doctors treat your cancer.
How is endometrial cancer staged?
- Surgical staging: Surgery is commonly performed for the treatment of endometrial cancer. Tissues removed during surgery will be sent to the laboratory and checked under a microscope for signs of cancer. This will help to determine if the cancer has spread.
- Radiological imaging staging may involve an MRI of the pelvis (magnetic resonance imaging) and/or CT scan and /or PET (positron emission tomography) scan to determine if cancer has spread.
Endometrial cancer is classified into four stages based on how much it has grown or spread:
- Stage 1: The cancer is only present in the uterus.
- Stage 2: The cancer is present in the uterus and cervix
- Stage 3: The cancer has spread outside the uterus and might be present in the vagina, fallopian tubes, ovaries and/or nearby lymph nodes.
- Stage 4:
- Stage 4A: The cancer has spread beyond the pelvic area and is present in the bladder and/or rectum.
- Stage 4B: The cancer has spread to organs, for example, the abdominal lining, lungs, liver and/or bones.
