All About Ovarian Cancer
What are the ovaries?
The ovaries are two small organs present only in women. They are located in a woman's pelvis, connected to her uterus (the organ where a baby grows and develops when a woman is pregnant) by the fallopian tubes. The ovaries are each about the size of a marble, and they can often be felt by your healthcare provider during the manual portion of a pelvic examination.
The ovaries are responsible for two important functions in a woman’s body: they produce female hormones and they produce eggs. Every month that a woman is fertile and not pregnant, her ovaries release a mature egg that travels into her uterus and has the potential to become fertilized. The ovaries also produce important hormones, namely estrogen and progesterone, which regulate a woman's menstrual cycles, influence the development of a woman's body during puberty, and keep a woman fertile.
What is ovarian cancer?
Ovarian cancer develops when cells in the ovaries begin to grow in an uncontrolled fashion. These cells also have the potential to invade nearby tissues or spread throughout the body. Large collections of this "out-of-control" tissue are often referred to as tumors. However, some tumors are not really cancer because they cannot spread or threaten someone's life. These are called benign tumors or masses. The tumors that can spread throughout the body or invade nearby tissues represent true invasive cancer, and are called malignant tumors.
The distinction between benign and malignant tumors is very important in ovarian cancer because many ovarian tumors are benign. Also, sometimes women (especially young women) can get ovarian cysts, which are collections of fluid in the ovaries that can occasionally grow large or become painful. However, ovarian cysts are not cancerous and should not be confused with ovarian cancer. Your healthcare provider may suggest that you have an ovarian cyst removed if it is becoming bothersome.
Cancers are characterized by the cells from which they originally form. The most common type of ovarian cancer is called epithelial ovarian cancer; it comes from cells that lie on the surface of the ovary known as epithelial cells. Epithelial ovarian cancer comprises about 90% of all ovarian cancers and usually occurs in older women. About 5% of ovarian cancers are called germ cell ovarian cancers and arise from the ovarian cells that produce eggs. Germ cell ovarian cancers are more likely to affect younger women. Another 5% of ovarian cancers are known as stromal ovarian cancers and develop from the cells in the ovary that hold the ovary together and produce hormones. These tumors can create symptoms by producing a large excess of female hormones. Each of these three types of ovarian cancer (epithelial, germ cell, stromal) contains many different subtypes of cancer that are distinguished based on how the cells look under a microscope. Discuss the exact category of ovarian cancer that you have with your provider so that you can get a sense of the particulars of your case.
A rare type of cancer, called primary peritoneal cancer, is a malignant tumor arising from the peritoneum, the lining of the abdominal cavity. It tends to behave similarly to ovarian cancer, and they can look identical under the microscope. The treatments used are often the same as those used for ovarian cancer. This type of cancer can develop in women with intact ovaries or in those who have had their ovaries removed.
What causes ovarian cancer and am I at risk?
In the U.S., it is estimated that 22,530 women will be diagnosed with ovarian cancer each year. Compared to other cancers, the incidence of ovarian cancer is quite rare.
Although there are several known risk factors for getting ovarian cancer, no one knows exactly why one woman gets it and another does not. The most significant risk factor for developing ovarian cancer is age. The older a woman is, the higher her chances are of developing ovarian cancer. The median age at diagnosis is 63, although women with genetic or family risk factors tend to be diagnosed with ovarian cancer at a younger age.
Other than age, the next most important risk factor for ovarian cancer is a family history of ovarian cancer. This is particularly important if your family members are affected at an early age. If your mother, sister, or daughters have had ovarian cancer, you have an increased risk for development of the disease. It is estimated that 7% to 10% of all ovarian cancers are the result of hereditary genetic syndromes. Genetic mutations that increase ovarian cancer risk include,
- Hereditary nonpolyposis colorectal cancer syndrome (HNPCC).
- Multiple endocrine neoplasia type 1 (MEN 1).
- Breast and ovarian cancer syndrome (associated with mutations in either the gene BRCA1 or BRCA2).
- Peutz-Jeghers syndrome.
- Gorlin syndrome.
- Site-specific ovarian cancer syndrome (which produces an increased risk for ovarian cancer alone).
It may be beneficial to test for mutations if a woman has a particularly strong family history of breast or ovarian cancer (meaning multiple relatives affected, especially if they are under 50 years old when they get the disease). Having a mutation doesn't necessarily mean a woman is going to be diagnosed with ovarian cancer, but it does greatly increase her chances above the general population. If a woman does have the mutation, she can get more rigorous screening, take preventive medications, or undergo prophylactic oophorectomies (preventive removal of your ovaries) to decrease her cancer risk. The decision to undergo genetic testing is a highly personal one that should be discussed with your healthcare provider and a genetic counselor who is trained in counseling patients about genetic testing and results.
Other risk factors include being overweight, never having children or having them later in life, using fertility treatments, taking hormone therapy after menopause, smoking, and alcohol use. Remember that all risk factors are based on probabilities, and even someone without any risk factors can still get ovarian cancer. Talk to your healthcare provider about your risk factors for ovarian cancer to understand his/her recommendations for screening and prevention.
How can I prevent ovarian cancer?
If you are a woman without a family history/genetic syndrome, the best way to prevent ovarian cancer is to alter whatever risk factors you have control over. For example, having children by age 30 and breastfeeding both reduce risk. Additionally, the use of oral contraceptives for 4 or more years is associated with a reduction in ovarian cancer risk in the general population. Bilateral tubal ligation and hysterectomy also decrease ovarian cancer risk. Keep in mind that any medication or surgical procedure has its own risks and should not be taken lightly.
Women who are carriers of one of the previously mentioned genetic syndromes face different decisions. They generally need to have more rigorous screening done for ovarian cancer. They may want to take a medication, such as tamoxifen, to reduce their risk, and some may elect to have their ovaries removed when they are still healthy (called a prophylactic oophorectomy). This should only be done when a woman is finished having children, and it can drastically reduce a woman's chances for developing ovarian cancer (but not reduce the risk to zero). Before a woman decides to do this, she should have genetic testing and a significant amount of counseling from a healthcare provider who has experience with genetic diseases.
While a diet high in animal fats has been implicated in ovarian cancer, a diet rich in fruits and vegetables may have a small preventive effect. It has been suggested that supplementation with vitamins A, C, and E may decrease your risk. However, there are no official nutritional recommendations that can be made to prevent ovarian cancer.
What screening tests are used for ovarian cancer?
If you are at average risk for ovarian cancer there are no recommended screening tests. However, you should have a gynecological exam as often as your provider suggest. Your provider may be able to feel your ovaries during the bi-manual portion of the exam, and if any abnormalities are felt, you can be referred for further tests. The major limitation to this method is that early ovarian cancers aren't usually felt on examination, and thus, are often missed.
There are a few other tests that are currently being studied for ovarian cancer screening. One is a blood test that looks for a protein named CA-125. CA-125 is a protein that is shed from damaged ovary cells, and is often elevated in ovarian cancer. There are a few problems with CA-125 as a screening test. It is elevated in many other diseases and conditions besides ovarian cancer, including other cancers, endometriosis, fibroids, menstruation, colitis, diverticulitis, pancreatitis, lupus, and inflammation of the lining of the lung or heart.
One possible way to use CA-125 for ovarian cancer screening is to check it and then re-check it 6 months later. If it drastically increases over this time, then it is more suggestive of ovarian cancer. The problem is that many patients without ovarian cancer will have elevated CA-125 levels and then have unnecessary further workup (called a false positive). You could also have a false negative result, where the CA-125 is not elevated, but there is actually cancer present and it therefore goes unrecognized.
Another investigational method for ovarian cancer screening is transvaginal ultrasound. Ultrasound is an imaging technique that uses sound waves that bounce off of tissues and provide a picture of whatever is being investigated. By inserting an ultrasound probe into a woman's vagina, healthcare providers can get a relatively good look at her ovaries. If the ovaries look suspicious, then further tests can be done. The biggest problem with using transvaginal ultrasound for ovarian cancer screening is the same problem as using CA-125; both tests cause too many healthy women to require unnecessary procedures because the tests are not specific enough for ovarian cancer. In studies, combining CA-125 and vaginal ultrasound did not lower the number of deaths related to ovarian cancer, and therefore are not routinely recommended for screening.
Women with a strong family history or those with a proven hereditary cancer syndrome may need to get more rigorous screening with serial CA-125 tests and/or transvaginal ultrasounds, though the benefit to this is not clear. Talk to your healthcare provider about your ovarian cancer risk, and the best way to go about screening in your particular case.
What are the signs of ovarian cancer?
Ovarian cancer has been called a "silent killer" because it was thought that symptoms did not develop until the disease was advanced. More recently, ovarian cancer experts found that this was not true, and most women had symptoms early on that were dismissed by themselves or their healthcare providers. Experts collaborated to develop the Ovarian Cancer Symptoms Consensus Statement, which describes important symptoms.
The symptoms that are more likely seen in women with ovarian cancer compared with healthy women include:
- Pelvic or abdominal pain.
- Difficulty eating or feeling full quickly.
- Urinary symptoms (urgency or frequency).
While these symptoms are more often due to other medical problems, women with ovarian cancer report that the symptoms persist and represent a change from their normal. The frequency and number of these symptoms are also key factors in the diagnosis.
Other possible symptoms include fatigue, indigestion, back pain, painful intercourse, constipation and menstrual irregularities. Women who experience these symptoms almost daily for more than a few weeks should see a healthcare provider (preferably a gynecologist) for evaluation.
How is ovarian cancer diagnosed?
The most common reason for a healthcare provider to suspect ovarian cancer is if he/she feels a mass during a pelvic examination. Ovarian cancer is a type of cancer that needs to be diagnosed and staged during a surgery. Often, the cancer is diagnosed and treated during the same procedure. Surgeries for ovarian cancer diagnosis and treatment should be done by a surgeon who specializes in gynecologic malignancies. Surgery is done so that samples of the mass and surrounding tissue can be biopsied and analyzed. A biopsy is the only way to know for sure if you have cancer, because it allows your healthcare providers to obtain cells that can be examined under a microscope. Once the tissue is removed, a healthcare provider called a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, the pathologist will characterize it by what type of tissue it arose from and what subtype of ovarian cancer it is, how abnormal it looks (called the grade), and whether or not it is invading surrounding tissues.
Although surgery is required for accurate staging, your providers may want to order some other tests to better characterize the mass/masses and look for distant spread. Tests like CT scans or MRIs can examine the pelvis and localized lymph nodes. Some patients with bony pain are referred for a bone scan, which is a test using a radioactive tracer to look for metastasis to any of the bones. You may also undergo a colonoscopy, which uses a lighted scope to examine your rectum and colon, or a barium enema in which dye is inserted into your rectum and an x-ray is taken. These tests are used to look for spread of the tumor to your colon. Each patient is unique, so the specific tests people get will vary; but overall, your providers want to know as much about your particular tumor as possible so that they can plan the best available treatments.
How is ovarian cancer staged?
In order to guide treatment and offer some insight into prognosis, ovarian cancer is staged into four different groups. The staging system used for ovarian cancer is the FIGO system (International Federation of Gynecologists and Obstetricians). Healthcare providers also use the TNM system (also called tumor - node - metastasis system). This system describes the size and local invasiveness of the tumor (T), which, if any, lymph nodes are involved (N), and if it has spread to other more distant areas of the body (M). This is then interpreted as a stage somewhere from I (one) denoting more limited disease to IV (four) denoting more advanced disease. Generally, the higher the stage, the more serious the cancer.
In addition to stage, the tumor grade will also be evaluated. This refers to how abnormal cells appear under a microscope. Low grade (or grade I) tumors appear the most like normal cells, whereas higher grade tumors (grades 3 and 4) appear very abnormal under the microscope. Higher-grade tumors may behave more aggressively than low-grade tumors. The staging system for ovarian and primary peritoneal cancer is also applied to malignant germ cell tumors, malignant sex cord-stromal tumors, and carcinosarcoma (malignant mixed Müllerian tumors).
The staging system is very complex, and the entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed.
How is ovarian cancer treated?
Almost all women with ovarian cancer will have some type of surgery in the course of their treatment. The purpose of surgery is first to diagnose and stage the cancer, as well as to remove as much of the cancer as possible. In early stage cancers (stage I and II), surgeons can often remove all of the visible cancer. Generally, women with ovarian cancer will have a hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes) as part of their operation. This is because there is always a risk of microscopic disease in both of the ovaries and the uterus. The only circumstance in which a woman may not have this entire operation is if she has a very early stage cancer (IA) that looks favorable under the microscope (grade 1). This is often the case with germ cell ovarian tumors. If a woman's tumor has these characteristics and she wishes to maintain the ability to have children, then the surgeon can remove only her diseased ovary and tube. Then, after she is done having children, she will need to have her uterus and the other tube and ovary removed. With any other stage or grade of tumor, or in patients finished with childbearing, the entire operation should be performed in order to provide the best possible chance for a cure.
Women who have more advanced disease (stage III or IV) will often have debulking surgeries. This means that the surgeon will attempt to remove as much disease as possible. Data collected in many studies has demonstrated that the more cancer that is removed, the better the long-term outcome for the patient.
Sometimes, a patient will have debulking surgery and then later the cancer will come back (recurrence). It may be useful to debulk the tumor a second time, particularly if it has been at least a year between the initial surgery and the recurrence. In patients with very advanced ovarian cancer, surgery may be used for palliation, meaning that patient is operated on with the intent of easing their pain or symptoms, rather than trying to cure their disease.
Operations for ovarian cancer should be performed by surgeons who are trained in dealing with gynecologic malignancies because there are special skills and techniques necessary to deal with these tumors.
Despite the fact that the tumors are removed during surgery, there is always a risk of recurrence because there may be microscopic cancer cells left that the surgeon cannot see or remove. In order to decrease a patient's risk of recurrence, a patient may receive chemotherapy. Chemotherapy is the use of anti-cancer medications that work systemically (throughout the entire body) and are administered either intravenously (directly into a vein), directly into the abdomen (intraperitoneal, “IP”) or orally (by mouth). The vast majority of patients with ovarian cancer should be offered chemotherapy as well as surgery (adjuvant chemotherapy). The higher the stage of cancer, the more important it is that you receive chemotherapy. Generally, only very early stage cancers (early stage I) that look favorable under the microscope (grade 1 or 2) can be treated with surgery alone. Any woman with a more advanced stage or grade ovarian cancer should be offered chemotherapy.
There are many different chemotherapy agents available, and treatments often combine several medications to create a regimen. For the treatment of ovarian cancers, chemotherapy is typically given intravenously (into a vein) or directly into the abdomen (intraperitoneal, "IP").
Some of the chemotherapy medications used in ovarian cancer treatment include: cisplatin, carboplatin, doxorubicin, topotecan, ifosfamide, doxorubicin liposomal, docetaxel, paclitaxel, altretamine, capecitabine, cyclophosphamide, etoposide, gemcitabine, irinotecan, melphalan, pemetrexed, and vinorelbine. Most regimens contain a platinum compound chemotherapy, such as cisplatin, and a taxane, such as paclitaxel or docetaxel.
Hormonal therapies including aromatase inhibitors (example: letrozole), tamoxifen, and luteinizing hormone-releasing hormone (LHRH) agonists (example: leuprolide acetate), are used more commonly in ovarian stromal type tumors, but not typically in epithelial ovarian cancer.
There are also some targeted agents used in the treatment of ovarian cancer including bevacizumab, rucaparib, niraparib and olaparib. Bevacizumab is used to stop blood flow to the tumor and works best when given with chemotherapy. Rucaparib, niraparib and olaparib are used only for certain subtypes of ovarian cancer associated with BRCA mutation. Your care team will evaluate the type of tumor you have to assess if targeted treatment may be an option after other first line methods of treatment have not been successful. Olaparib and rucaparib can also be used to treat advanced cancer with or without mutations in the BRCA gene.
Intraperitoneal (IP) chemotherapy is given directly into the abdomen through a catheter, allowed to "dwell,” or remain in the abdomen for a while, coating the area in chemotherapy. This allows concentrated doses of the chemo to be in direct contact with the cancer cells in the abdominal cavity. After several hours, fluid is drained from the abdomen, releasing the remaining chemotherapy from the abdomen. It is typically used in stage III cancers where the tumor has been optimally debulked (leaving nothing larger than 1cm). This can also be done at the time of the debulking surgery.
There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your health, your personal values and wishes, and potential impact of side effects, you can work with your healthcare providers to come up with the best regimen for your cancer and your lifestyle.
Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. It comes from an external source, and it requires patients to come in 5 days a week for several weeks to a radiation therapy treatment center. The treatment takes just a few minutes and is painless. Radiation therapy is occasionally combined with surgery in patients who have stage II tumors with low bulk disease. Radiation can also be used to ease the pain of metastases and/or to stop tumors from bleeding. Generally, healthcare providers try to limit the amount of radiation that your vital organs receive, and don't like to treat large portions of the bowel and pelvis for this reason. This makes radiation less useful in ovarian cancer, where disease is often diffusely spread throughout the abdomen and pelvis. A radiation oncologist can answer questions about the utility, process, and side effects of radiation therapy in your particular case.
Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.
Follow-up Care and Survivorship
Once a patient has been treated for ovarian cancer, they need to be closely followed for a recurrence. At first, you will have follow-up visits fairly often, usually every few motnhs. The longer you are free of disease, the less often you will have to go for checkups. Your healthcare provider will tell you when he or she wants follow-up visits, CA-125 levels, pelvic ultrasounds and/or CT scans, depending on your case. Your healthcare provider will also perform pelvic examinations. It is very important that you let your healthcare provider know about any symptoms you are experiencing and that you keep all of your follow-up appointments.
Fear of recurrence, relationships and sexual health, financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by ovarian cancer survivors. Your healthcare team can identify resources for support and management of these challenges faced during and after cancer.
Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.
Resources For More Information
National Ovarian Cancer Coalition
Through national programs and local Chapter initiatives, the NOCC's goal is to make more people aware of the early symptoms of ovarian cancer. In addition, the NOCC provides information to assist the newly diagnosed patient, to provide hope to survivors, and to support caregivers.
Ovarian Cancer National Alliance
Connects survivors, women at risk, caregivers and health providers with the information and resources they need.
Pregnant with Cancer
Dedicated to providing women diagnosed with cancer while pregnant with information, support and hope.
Foundation for Women’s Cancers
The Foundation offers comprehensive information by cancer type that can help guide you through your diagnosis and treatment. They also offer the ‘Sisterhood of Survivorship’ to connect with others facing similar challenges.
Appendix: Complete Fallopian Tube & Ovarian Cancer Staging
AJCC, Cancer Staging Manual, 8th Edition
Primary Tumor (T)
Primary tumor cannot be assessed
No evidence of primary tumor
Carcinoma in situ (limited to tubal mucosa)
Tumor limited to the ovaries (one or both) or fallopian tubes
Tumor limited to one ovary or tube, no tumor on surface; no malignant cells in peritoneal washings or ascites
Tumor limited to both ovaries or tubes, no tumor on surface; no malignant cells in peritoneal washings or ascites
Tumor limited to one or both tubes with any of the following:
Capsule ruptured before surgery or tumor on ovary or tube surface
Malignant cells in ascites or peritoneal washings
Tumor involves one or both Fallopian tubes with pelvic extension
Extension and/or implants on the uterus and/or fallopian tube(s) and/or ovaries
Extension to and/or implants on other pelvic structures
Tumor involves one or both fallopian tubes, or primary peritoneal cancer with peritoneal metastasis outside the pelvis and/or metastasis to retroperitoneal lymph nodes
Microscopic peritoneal metastasis outside the pelvis with or without positive retroperitoneal lymph nodes
Macroscopic peritoneal metastasis outside the pelvis 2cm or less in greatest dimension with or without positive retroperitoneal lymph nodes
Peritoneal metastasis outside the pelvis and more than 2cm in diameter with or without positive retroperitoneal lymph nodes
Regional Lymph Nodes (N)
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Isolated tumor cells, < 0.2mm, in regional lymph nodes
Positive retroperitoneal lymph nodes only
Metastasis < 10mm in greatest diameter
Metastasis > 10mm in greatest diameter
Distant Metastasis (M)
No distant metastasis
Pleural effusion with positive cytology
Liver or splenic metastases, metastases to organs or lymph nodes outside the abdomen, involvement of the intestine
Pleural effusion with positive cytology
Liver or splenic parenchymal metastases, metastases to extra-abdominal organs, transmural involvement of intestine
Nx, N0, N1
Nx, N0, N1
Nx, N0, N1
American Cancer Society. Ovarian Cancer. 2019. https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html
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