Epithelial Ovarian Cancer / Fallopian Tube Cancer/ Primary Peritoneal Cancer (PPC) Treatments in Singapore
What type of epithelial ovarian cancer treatment will I need?
Oncologists treat epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer (PPC) in a very similar way.
Treatment options and recommendations depend on several factors, including the stage of cancer, the subtype of ovarian cancer, treatment side effects, patient’s overall health and personal preferences.
Ovarian cancer is treated by one or a combination of treatments, which include:
- Anti-cancer drug therapy
- Targeted therapy
- Hormonal therapy
The mainstay treatment of epithelial ovarian cancer comprises a combination of surgery and chemotherapy. Non-chemotherapy drug treatments have been added to the armamentarium to treat ovarian cancers in recent years. PARP inhibitor, a new type of targeted cancer therapy, is transforming the way oncologists treat ovarian cancer.
Oncologists at OncoCare with Clinical Interests in Ovarian Cancers
OncoCare is the leading ovarian cancer care provider in Singapore. Our specialists have extensive experience in diagnosing and treating all types of ovarian cancers as well as other types of cancers such as breast, cervical, colon, hepatobiliary, and liver. We offer many types of ovarian cancer treatments in Singapore to suit our patients’ needs.
Treatments for Ovarian Cancer: Surgery
Ovarian cancer surgery has two purposes:
- To remove the cancer
- To stage the cancer
Early ovarian cancer confined to the ovary:
Surgery involves the removal of the uterus (hysterectomy), the ovaries, the fallopian tubes (salpingo-oophorectomy), the omentum (a layer of fatty tissue that covers our abdominal organs) and the lymph nodes around the tumour. The abdominal cavity will also be “washed” with salt water and this fluid, together with the tissues removed during surgery, are checked under a microscope for cancer cells. This helps to determine if cancer has spread outside the ovary and the extent of cancer spread, which is also known as cancer staging.
Advanced ovarian cancer (cancer spread outside the ovary):
The goal of surgery is to remove as much of the tumour as possible (“debulk”) and avoid leaving any cancer behind. This type of surgery is called debulking surgery. Women whose ovarian cancer has been completely removed has a much better outcome than those left with cancers after surgery.
If I have ovarian cancer, can I still get pregnant?
For certain stage I early epithelial ovarian cancer, surgical removal of the ovary affected by the cancer with preservation of the uterus and the normal ovary may be an option. Premenopausal women who desire to preserve their fertility can discuss with their ovarian cancer specialist if they are suitable for fertility preservation surgery.
Treatments for Ovarian Cancer: Drug Therapy
Unlike surgery which targets cancer in specific areas of our body, drug therapy enters our blood stream, and 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.
The main types of drug therapy used in ovarian cancer treatments are:
- Targeted Therapy
- Hormonal Therapy
Treatments for Ovarian Cancer: Chemotherapy
Chemotherapy is a drug treatment that kills ovarian 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.
Ovarian cancers are highly responsive to chemotherapy. Many chemotherapy drugs are used in ovarian cancer treatments in Singapore. The commonly used drugs include carboplatin, cisplatin, paclitaxel, pegylated liposomal doxorubicin and gemcitabine. These drugs can be used on its own, or more commonly, in combination.
Modes of Chemotherapy Administration:
- Intravenous infusion (IV): Chemotherapy for ovarian cancer is most commonly given as an infusion into a vein
- Pills (by mouth): some chemotherapy drugs can be taken by mouth
- Chemotherapy infused into the abdominal cavity:
- Intraperitoneal chemotherapy (IP): Chemotherapy is sometimes delivered directly into the abdominal cavity where ovarian cancer commonly spreads to.
- HIPEC: During ovarian cancer surgery, heated chemotherapy drugs can be delivered directly into the abdominal cavity
IP and HIPEC chemotherapy cause more severe side effects than IV or oral chemotherapy but may work better for some women. Research is underway to find out which women are more likely to benefit from this type of treatment.
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 ovarian cancer specialist will provide you with an in-depth discussion of the chemotherapy drugs available in Singapore, treatment schedule and the relevant side effects so you can better understand them.
Treatments for Ovarian Cancer: Targeted Therapy
Each and every ovarian tumour has a unique set of genes, proteins or other substances that drives cancer growth. Drugs can be specially designed to block these to stop cancer growth. These drugs are called targeted therapy, and 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 ovarian cancer treatments include:
- PARP inhibitors
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 specific genes or proteins that drive your cancer growth. This information can help your ovarian cancer specialist select the most appropriate targeted therapy for your cancer.
Side effects of targeted therapy are dependent on the type of 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.
PARP inhibitor is a new and exciting treatment for ovarian cancer. It has revolutionized the way we treat ovarian cancer. It is an oral (pill) targeted therapy. Olaparib, niraparib and rucaparib are examples of PARP inhibitors used in the treatment of ovarian cancer.
How do PARP inhibitors work?
The DNA (genetic material) in our cell is constantly being damaged by, for example UV exposure or radiation in the environment. The damaged DNA needs to be repaired so that the cell can survive.
PARP is a protein found in our cells. It helps damaged cells to repair themselves. PARP inhibitors prevent the PARP from doing its repair work, causing the DNA damage to worsen. A more complex repair system, the homologous repair system, is now needed for DNA repair. The homologous repair system may be faulty or defective in some ovarian cancers and these cancers are called homologous recombinant deficient or HRD.
PARP inhibitors may be more effective in HRD ovarian cancer. Blocking the PARP protein with a PARP inhibitor drug makes it even harder for these HRD cancers to repair themselves and they die.
Homologous Recombinant Deficient (HRD) ovarian cancers
HRD is present in 50% of ovarian cancers and is more common in the high grade serous subtype. HRD is caused by faults (or mutations) in a number of genes, but most commonly, in the BRCA1 or BRCA2 genes.
Testing for HRD and/or BRCA mutation:
- Testing the tumour for HRD and BRCA1/2 mutation
- Testing the tumour for BRCA1/2 mutation
- Testing (genetic) for germline BRCA1/2 mutation present in hereditary ovary cancer
Your ovarian cancer specialist may recommend one or a combination of the above tests.
Side effects of PARP inhibitors are generally mild and may include tiredness, loss of appetite, anaemia, diarrhoea and muscle ache. Uncommon but serious side effects may include lung inflammation and slight increased risk of developing a different type of cancer.
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 ovarian cancer include bevacizumab, which is usually combined with chemotherapy.
Very rarely, ovarian 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.
Some ovarian cancers contain estrogen and/or progesterone hormone receptors. Hormone receptors are commonly found in low grade ovarian cancers, such as low grade serous ovarian cancer and low grade endometrioid type ovarian cancer. Hormone therapy can slow down or stop the growth of these hormone-dependent cancers by reducing the estrogen levels.
Hormone therapy used in the treatment of ovarian cancer are also commonly used in the treatment of hormone-dependent breast cancer and includes:
- Aromatase inhibitor (example letrozole and anastrazole)
Treatment based on Stages of Ovarian Cancer
Stage 1 or Stage 2 Epithelial Ovarian Cancer / Fallopian Tube Cancer / PPC:
Surgery is the mainstay treatment for women with stage I and II cancers.
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 chemotherapy are needed to lessen the chance of your cancer coming back. Most women with ovarian cancer will require chemotherapy after their surgery. Some women with very early stage I may not need chemotherapy.
Chemotherapy Treatment, commonly includes a drug called carboplatin. Adding a second drug, called paclitaxel, to carboplatin seems to work better than using carboplatin alone. The typical course of this chemotherapy regimen involves 6 cycles of treatment over a 18-week period with a rest period in-between treatments to allow our body to recover before the next treatment. For some subtypes of stage I ovary cancer, 3 cycles of chemotherapy may be adequate. This chemotherapy regimen is given as intravenous infusions (IV) in the comfort of the clinic. Side effects are generally manageable. But for women who cannot tolerate paclitaxel, alternative chemotherapy drugs can be considered.
Your oncologist will provide you with an in-depth discussion of chemotherapy treatment, schedule and side effects so you can understand your treatment better.
Stage 3 or Stage 4 Epithelial Ovarian Cancer / Fallopian Tube Cancer / PPC:
For advanced ovarian cancers, treatment comprises both debulking surgery and chemotherapy. The goal of debulking surgery is to remove all cancers as the amount of cancers left behind has an adverse impact on cancer outcome. Following debulking surgery, women will require chemotherapy to reduce the chance of cancer coming back.
If the cancer is deemed to be too extensive to be removed completely with debulking surgery, or if the woman is not physically fit for surgery, oncologist may recommend a short course of chemotherapy, known as neoadjuvant chemotherapy, to shrink down the cancer first before surgery. This helps to improve the success of the debulking surgery.
Following surgery and chemotherapy treatments, some women may benefit from maintenance therapy to improve cancer control.
- Debulking surgery
- Adjuvant chemotherapy is chemotherapy given after surgery to reduce the chance of cancer coming back. Chemotherapy is recommended in advanced ovarian cancer even if your surgery was successful at removing all visible cancers as tiny cancers are likely to be still present in the body that we are not able to detect with current tests. Typically, 6 cycles of carboplatin and paclitaxel chemotherapy are recommended.
- Neoadjuvant chemotherapy is chemotherapy given before surgery to shrink down the cancers prior to surgery so that the surgery has a better chance of removing all cancers. Usually, 2 to 3 cycles of carboplatin and paclitaxel chemotherapy are given before surgery.
- Maintenance Therapy
Following initial treatment with surgery and chemotherapy, there is a high likelihood that advanced ovarian cancer may return. Maintenance therapy aims to kill any cancer cells that remain after surgery and chemotherapy but are too small to be detected with current tests. The goal is to reduce the chance of cancer coming back.
Types of Maintenance Therapy:
Anti-angiogenic: Bevacizumab, an anti-angiogenic can be used as maintenance therapy in advanced ovary cancer. It is given as a short intravenous infusion (IV) once every 3 weeks in the outpatient clinic for a treatment period of 12 months.
PARP inhibitors work better for cancers which are homologous repair dependent (HRD). It can be used on its own or together with bevacizumab. Cancers which are not HRD may also benefit from PARP inhibitor treatment but the benefit is smaller. PARP inhibitor comes in pill-form and is taken daily for a period of two to three years.
Recurrent Epithelial Ovarian Cancers/ Fallopian Tube Cancer / PPC:
Recurrent cancers are previously treated cancers that have come back. Surgery is sometimes recommended, but the mainstay treatment is drug therapy, in particular chemotherapy. Targeted therapy and hormonal therapy may also be helpful.
Chemotherapy: These cancers are responsive to chemotherapy. There are a number of ovarian cancer chemotherapy drugs that can be used. The commonly used drugs include carboplatin, paclitaxel, pegylated liposomal doxorubicin and gemcitabine. The choice of chemotherapy drugs depends on what chemotherapy drugs had already been used and how well the previous chemotherapy worked. The longer the cancer stayed away after a course of chemotherapy, the greater the chance of it responding to a subsequent chemotherapy. Generally, if at least 6 months has passed since any chemotherapy, carboplatin chemotherapy is re-used, usually together with another ovarian cancer chemotherapy drug.
- Bevacizumab may be given with chemotherapy
- PARP inhibitor:
- Maintenance treatment after ovarian cancer has reduced in size following carboplatin-containing chemotherapy
- Treatment of recurrent ovarian cancer that is BRCA mutated or HRD
Hormonal therapy such as letrozole, anastrazole or tamoxifen may benefit women with hormonally-dependent cancers. Low grade serous ovarian cancer and low-grade endometrioid ovarian cancers are more likely to be dependent on hormones for their growth.
What is Ovarian Cancer?
Ovarian Cancer is a type of cancer that begins in the ovary. Each woman has two ovaries, each one is the size of an almond located on each side of the womb (uterus). The ovary produces eggs for reproduction as well as the female hormones, estrogen and progesterone.
Types of Ovarian Cancer:
There are 3 main types of ovarian cancer:
1. Epithelial ovarian cancer
The most common type of ovarian cancer. About 90- 95% of all ovary cancers are epithelial ovary cancer. These cancers arise from the cells that line the outer surface of the ovary. It is more common in postmenopausal women.
2. Germ cell ovarian cancer
These cancers begin in the eggs (also known as germ cells) and affect mainly young women. They are rare. With appropriate treatment, the outlook is very good.
3. Stromal cell ovarian cancer
These cancers begin in the ovary tissues that produce the female hormones estrogen and progesterone. These are rare cancers.
These three types of ovarian cancer arise from the ovary but they are distinctly different cancers and require different types of treatment.
Fallopian tube cancer is a cancer that begins in the fallopian tube, the duct that carries eggs from the ovaries to the uterus. Women who have BRCA gene mutations are more at risk.
Primary peritoneal cancer (also known as PPC) is a cancer that begins in the tissue lining the inside of the abdomen and pelvis. This lining is called the peritoneum.
Fallopian tube cancer and primary peritoneal cancer are rare cancers. They behave similarly to epithelial ovarian cancer. Ovarian cancer specialists treat epithelial ovarian cancer, fallopian tube cancer and PPC in a very similar way.
Epithelial Ovarian Cancer: Symptoms and Signs
What are the warning symptoms and signs of Epithelial Ovarian Cancer?
Ovarian cancer is the deadliest of the gynaecological cancers and is also known as the “silent killer”. 3 out of 4 of these cancers are diagnosed at an advanced stage. The ovaries are hidden deep in the lower abdomen (pelvis) making it difficult to detect early. The symptoms caused by ovarian cancer are often ignored as they can be commonly confused with other less serious conditions such as indigestion and menstrual symptoms.
The symptoms and signs of ovarian cancer may include:
- Abdominal or pelvic pain
- Eating difficulties or early satiety (quickly feeling full)
- Frequent and urgent urination
- Enlarging waistline due to build-up of cancer-containing fluid in the abdomen (also known as ascites)
- Extreme exhaustion or fatigue
- Acid reflux
- Pain during intercourse
- Changes in menstruation
It is crucial to pay attention to your body and know what is normal for you. If you have any of the above symptoms that lasts for two weeks or longer, please consult an ovarian cancer specialist in Singapore for treatment. They may be caused by something other than cancer, but it is best to get it checked as finding cancer can improve treatment success.
Epithelial Ovarian Cancer: Who is At Risk?
Anything that enhances your chances of having ovarian cancer is considered a risk factor. However, having one or more risk factors does not guarantee that you will get the condition. Some individuals who develop ovarian cancer may have a combination of the below risk factors or none at all.
- Ageing: The majority of ovarian malignancies appear after menopause. Women aged 63 and up account for half of all ovarian cancer cases.
- Family History: If your family member has or previously had ovarian cancer, your chances of getting it are higher. This is because ovarian cancer can be caused by a hereditary mutation in particular genes that results in a family cancer syndrome that raises the risk of the disease.
- History of Breast Cancer: If you’ve had breast cancer, your chances of getting ovarian cancer are likely higher. Some of the same reproductive risk factors that increase the risk of ovarian cancer may also increase the risk of breast cancer.
- Obesity or Being Overweight: Obese women (those with a BMI of at least 30) are more likely to get ovarian cancer.
- Pregnancy and Childbirth: Ovarian cancer is more likely to appear in women who have their first full-term pregnancy after the age of 35 or those who have never carried a baby to term.
- Post Menopause Hormone Replacement: Women who take estrogens alone or in combination with progesterone after menopause have a higher risk of ovarian cancer than women who have never used hormones.
- Smoking: Smoking increases the chance of mucinous ovarian cancer.
- Endometriosis: women with endometriosis have a slightly higher risk of certain types of ovarian cancer, namely clear cell and endometrioid ovarian cancer.
Is my ovarian cancer hereditary?
Ovarian cancer can run in families. About 1 in 5 ovarian cancers are hereditary, mostly due to the Hereditary Breast and Ovarian Cancer syndrome, and less commonly due to Lynch syndrome. We can inherit a damaged or faulty (mutated) gene from either of our parents which puts us at increased risk of ovarian cancer.
Hereditary Breast and Ovarian Cancer Syndrome (HBOC)
15% of all ovarian cancers occur in women with HBOC. The genes responsible are called breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2). The BRCA genes play an important role in repairing the damaged DNA in our body. A fault (or mutation) in these genes cause a build-up of DNA damages which can lead to a higher risk of developing certain cancers, such as cancer of the ovary, breast, pancreas and prostate.
Up to 2% of all ovarian cancers occur in women with Lynch syndrome. The genes responsible are called mismatch repair genes. People with Lynch syndrome are also at risk of cancers of the endometrium (uterus), colon, gastrointestinal tract (stomach, pancreas, liver) and urinary tract.
Why is it important to know if my ovarian cancer is hereditary?
Family members are also at risk of carrying the gene mutations 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 hereditary cancer syndromes.
Knowing if one’s ovarian cancer is associated with HBOC or Lynch syndrome may impact on how we treat the cancer. Ovarian cancer with BRCA mutation responds particularly well to PARP inhibitor. Ovarian cancer associated with Lynch syndrome may respond exceptionally well to immunotherapy treatment due to their faulty mismatch repair genes.
When do we suspect hereditary cancer syndrome?
We suspect cancer may be hereditary in nature when there are multiple family members with cancers, especially if these cancers occur at a young age (before the age of 50). Family history on its own, however, is not reliable as some women with hereditary type of ovarian cancer may not necessarily have a strong history of cancer in the family.
How to test for HBOC or Lynch syndrome?
To confirm the diagnosis, we need to do genetic testing. This involves blood test (or saliva) to check for mutations in the BRCA1/2 or the Lynch syndrome genes.
Before embarking on genetic testing, we recommend that you speak to your doctor as they will be able 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 Ovarian cancer?
If your doctor suspects ovarian cancer, he or she may perform the following tests:
- Physical examination to check for signs of disease, such as abnormal lumps.
- Imaging tests which may include:
- Ultrasound scan to determine the size and appearance of your ovaries
- CT scan or PET-CT scan to check if cancer has spread outside the ovaries
- Blood test for CA125 tumour marker: CA125 is a protein produced by some ovarian cancers. This test cannot tell you if you have cancer. Some women with ovarian cancer can have a normal CA125.
Your doctor cannot be certain of your diagnosis until you go through surgery to remove the ovary which is then checked under a microscope for cancer cells. Fluid from the abdomen (ascites), if present, can also be removed and tested for the presence of cancer.
Histologic Subtypes of Ovarian Cancer
Epithelial ovarian carcinomas can be divided into 5 different types based on their appearance under the microscope, also known as histologic subtypes.
The 5 most common subtypes of ovarian cancer are:
- High grade serous ovarian cancer
The most common subtype of epithelial ovarian cancer and represents 2 out of 3 epithelial ovarian cancer. They are more likely to have spread outside the ovaries by the time they are diagnosed. These cancers respond very well to chemotherapy
- Endometrioid ovarian cancer
Can be further divided into “low-grade” or “high-grade” cancer. The behaviour of high grade endometrioid ovarian cancer is similar to high grade serous ovarian cancer. The low-grade cancers tend to be slower growing and may respond well to hormonal therapy.
- Clear Cell ovarian cancer
More common in Asians than Caucasians. Most of these cancers are detected early.
- Mucinous ovarian cancer
Rare. Most women are under the age of 40. Most of these cancers are detected early.
- Low grade serous ovarian cancer
Uncommon. Slow growing cancer and may respond well to hormonal therapy
Ovarian Cancer Staging: Has my cancer spread?
After ovarian cancer has been diagnosed, tests are done to find out if cancer is still confined to the ovary, 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 ovarian cancer staged?
- Surgical staging: Surgery is commonly performed for the treatment of ovarian 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 cancer has spread.
- Radiological imaging staging: CT or PET (positron emission tomography) scan to determine if cancer has spread.
Ovarian cancer is classified into four stages based on how much it has grown or spread:
- Stage 1: The cancer is only present in one or both ovaries.
- Stage 2: The cancer is present in the pelvic organs such as the uterus, the bladder, the rectum and /or the tissue lining the pelvis.
- Stage 3: The cancer is present in the lymph nodes in the abdomen and / or has spread outside the pelvis to abdominal tissues such as the omentum, the tissue lining the abdominal cavity and /or surfaces of the intestines or liver.
- Stage 4: The cancer has spread to organs such as the lungs, the liver and/or the bones.