by Dr. C.H. Weaver M.D. Medical Editor 6/2022
Ovarian cancer is a common malignancy in women in the United States, with about 23,000 individuals diagnosed each year.1 The ovaries are small female reproductive organs that reside in the pelvis. The ovary makes female hormones and stores all of the egg cells, which are released once a month during ovulation. There are two ovaries, one on each side of the uterus, or womb. Egg cells are delivered from the ovaries to the uterus by hollow organs called fallopian tubes.
Some ovarian tumors are benign (not cancerous). Malignant (cancerous) ovarian tumors can originate from the surface epithelium (cells covering or lining the ovaries), germ cells (cells that are destined to form eggs), or sex cord-stromal cells (cells that secrete hormones and connect the different structures of the ovaries). The majority of ovarian cancers develop from cells in the lining of the ovary. These are referred to collectively as epithelial ovarian cancers. In this treatment overview, the term ovarian cancer refers to epithelial ovarian cancer. Benign ovarian tumors and ovarian germ cell tumors are not further discussed in this section.
Common Epithelial Tumors: Common epithelial cancers that start in the surface epithelium account for the majority of ovarian cancers and include the following types:
- Serous: This is the most common type of ovarian cancer and accounts for about 40% of common epithelial cancers. It occurs most often in women between the ages of 40 and 60.
- Endometrioid: This type of ovarian cancer accounts for about 20% of common epithelial cancers and is associated with endometriosis in 5% and endometrial carcinoma (cancer of the womb) in 20% of cases. It occurs most often in women between the ages of 50 and 70.
- Mucinous: Mucinous cancers account for 6-10% of common epithelial ovarian cancer and most often affect women between 30 to 50 years of age.
- Clear Cell Carcinoma: Clear cell carcinomas account for about 5% of common epithelial tumors and most often affect women between age 40 and 80.
- Undifferentiated Cancers: The remaining 15% of common epithelial cancers are referred to as undifferentiated tumors because their exact cell of origin cannot be determined under a microscope.
Borderline Ovarian Tumors: These ovarian tumors of low malignant potential are a subgroup of common epithelial tumors that occur in 10-15% of cases. These tumors are between cancerous and non-cancerous in nature. They originate on the surface of the ovary, but do not invade deeper tissues of the ovary. They have a better prognosis (prediction about the possible outcome of a disease) and cure rate than invasive ovarian tumors.2-4
Symptoms and Signs of Ovarian Cancer
Because epithelial ovarian cancers begin deep in the pelvis, they often do not cause any symptoms until they are at an advanced stage. Furthermore, many of the symptoms of ovarian cancer are hard to differentiate from symptoms experienced by women who do not have ovarian cancer, such as back pain, fatigue, abdominal bloating, constipation, vague abdominal pain, and urinary symptoms. Because of the lack of specificity of early ovarian cancer symptoms the majority of women (roughly 70%) already have advanced cancer at the time of diagnosis.1-3 Ovarian cancer is often originally suspected in women when their physician finds an abnormal pelvic growth during an internal pelvic examination. Ovarian cancer may spread to the lining of the abdominal cavity and lead to the buildup of fluid inside the abdomen, called ascites.
- Back pain
- Abdominal bloating
- Vague abdominal pain
- Urinary symptoms
- Irregular bowel movements
Risk factors for Ovarian Cancer
Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get colon cancer and not having risk factors doesn’t mean that you will not get cancer, it simply means that you are at greater risk than normal to develop the cancer. Risk factors for ovarian cancer include the following:
- Having a family history of breast or ovarian cancer in a first degree relative (parent, sibling, or child) with breast cancer gene mutations, referred to as BRCA1 and BRCA2.
- Having inherited changes in certain genes associated with familial colon cancer and polyposis syndromes. Lynch syndrome
- Having a personal history of previous colon, rectal, or ovarian cancer.
- Older age is also a risk factor for most cancers. The chance of getting cancer increases’ as you get older
Diagnosis and Tests for Ovarian Cancer
Doctors use many tests to find, or diagnose, cancer. They also do tests to learn if cancer has spread to another part of the body from where it started. A biopsy is the only certain way to confirm a diagnosis of ovarian cancer. When performing a biopsy, the doctor takes a sample of tissue for testing in a laboratory. The doctor may recommend some or all of these tests to help make a diagnosis and further evaluate the cancer.
Accurate surgical evaluation of ovarian cancer is necessary for nearly all patients and can only be accomplished during a laparotomy to determine the stage of the cancer and to remove as much cancer as possible. Patients who have already undergone surgery for ovarian cancer and know their stage of cancer may select from the options below. Patients who have not yet undergone surgery can learn more at Surgical Management of Ovarian Cancer.
In addition to an initial laparotomy to diagnose ovarian cancer, determining the extent of the spread or stage of the cancer requires a number of tests and is ultimately confirmed by surgical removal of the cancer and exploration of the abdominal cavity. The following tests may be used to evaluate ovarian cancer.
- Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body. This method is more sensitive and precise than an X-ray.
- Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue. MRI gives better pictures of tumors located near bone than CT, does not use radiation as CT does, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the tumor.
- Ultrasound: Ultrasound is a technique that uses sound waves to differentiate tissues based on varying tissue density. Ultrasound can be used transdermally (through the skin), transrectally (using a small probe inserted into the rectum) or intraoperatively (during surgery or during colonoscopy, which is called endoscopic ultrasound). Transrectal or endoscopic ultrasound may be used in conjunction with CT or MRI scans to help with staging.
- CA-125: Elevated levels of the protein CA-125 in the blood have been associated with ovarian cancer. However, the presence of elevated levels of CA-125 in the blood does not always indicate the presence of ovarian cancer because CA-125 levels can be elevated in a number of other conditions. The normal level of CA-125 is less than 35 units per milliliter in the blood. In general, the higher the level of CA-125 found, the greater the chance of having ovarian cancer, especially for women past menopause. Once a diagnosis of ovarian cancer has been established, the level of CA-125 in the blood is a useful indicator of cancer growth during or after treatment.
Genomic or Biomarker Testing - Precision Cancer Medicine
Not all ovarian cancer cells are alike. They may differ from one another based on what genes have mutations.The purpose of precision cancer medicine to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the ovarian cancer cells with specific abnormalities, leaving normal cells largely unharmed.
By testing an individual’s ovarian cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines. All women diagnosed with ovarian cancer should undergo NGS testing for BRCA, HRD and other mutations.
Ovarian Cancer Stages
Following surgical removal and staging of ovarian cancer, a final stage will be given. A Roman numeral from I to IV describes the stage and a letter from “A” to “C” describes a sub-stage. All treatment information concerning ovarian cancer is categorized and discussed by the stage.
Stage I: Cancer is found only in one or both of the ovaries. Cancer cells may also be found in abdominal fluid, or ascites.
Stage II: Cancer is found in the ovaries and has spread to the uterus (womb), the fallopian tubes, or other areas within the pelvis. Cancer cells may also be found in abdominal fluid, or ascites.
Stage III: Cancer is found in the ovaries and has spread to other body locations within the abdomen, such as the surface of the liver, intestine or lymph nodes.
Stage IV: Cancer is found in the ovaries and has spread outside the abdomen or inside of the liver.
Recurrent or Refractory: Recurrent disease means that the cancer has returned (recurred) after it has been treated. Refractory disease means the cancer is no longer responding to treatment.
Screening and Prevention of Ovarian Cancer
Information about the prevention of cancer and the science of screening appropriate individuals at high risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.
Understanding DNA Damage Response or DDR and Cancer Treatment
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Ovarian cancer has the highest mortality rate of all gynecologic cancers. It is the fifth leading cause of cancer death among U.S. women, and it is projected that 22,500 women will be diagnosed in 2021 and over 16,000 will succumb to their cancer.1
The causes of ovarian cancer are poorly understood. However, researchers have evaluated risk factors associated with ovarian cancer. A few risk factors have been identified and others are suspected.
The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer
Heredity and Genetic Factors for Ovarian Cancer
An estimated 5-10% of ovarian cancers are due to inherited gene mutations. Women with mutations in the BRCA1 or BRCA2 genes, for example, have a high risk of both breast and ovarian cancer. Estimates of the lifetime risk of ovarian cancer among women with a BRCA1 or BRCA2 gene mutation range from 10% to 68%.2 Preventive surgery to remove the ovaries before cancer develops is one approach to reduce the risk of ovarian cancer among women at high risk of the disease.
In addition, even among women without a BRCA1 or BRCA2 mutation, those with a family history of ovarian cancer (particularly in a close relative such as a mother, sister, or daughter) are at increased risk of developing the disease.
Environmental or Non-Genetic Factors
Factors linked with a reduced risk of ovarian cancer include use of oral contraceptives; tubal sterilization (tubal ligation); and an increasing number of full-term pregnancies.3 Breastfeeding has also been linked with a reduced risk of ovarian cancer.4
A factor that may increase the risk of ovarian cancer is use of postmenopausal hormones.5,6
As researchers continue to explore environmental and behavioral risk factors for ovarian cancer, it’s increasingly becoming clear that some factors are linked only with specific types of ovarian cancer (serous, endometrioid, mucinous, etc). For example, smoking has been reported to increase the risk of mucinous ovarian cancer but not other types of ovarian cancer.7 Additional research along these lines may provide important clues to the causes of ovarian cancer, and may also suggest additional approaches to prevention.
Prevention of Ovarian Cancer
Research into the risk factors for ovarian cancer has provided important clues about steps women can take to reduce their risk of the disease.
Removal of the Ovaries: In women who have a strong family history of ovarian cancer or the presence of a BRCA1 or BRCA2 mutation, removal of the ovaries before cancer develops (prophylactic oophorectomy) can greatly reduce ovarian cancer risk. Surgery doesn’t completely eliminate ovarian cancer risk because some cells remain behind after surgery. Removal of the ovaries also reduces the risk of breast cancer since some breast cancers don’t grow well without the hormones produced by the ovaries. Women with a BRCA1 or BRCA2 alteration who have had their ovaries removed have about half the risk of developing breast cancer as those who have not had their ovaries removed.7
Following removal of the ovaries, women will likely experience menopausal symptoms such as hot flashes. These symptoms are often more severe in women who have their ovaries removed surgically than in women who reach menopause naturally. Removal of the ovaries also means that a woman will be unable to have children. Some women may therefore choose to postpone surgery until after they’ve completed their families. Ovarian cancer in BRCA1 and BRCA2 carriers most often occurs after age 40.8,9
Oral Contraceptives: Oral contraceptives reduce the risk of ovarian cancer, and longer-term use provides a greater reduction in ovarian cancer risk than shorter-term use.10 Because oral contraceptives can have a range of health effects, however, decisions about the use of oral contraceptives should be made on an individual basis, in consultation with a health care professional.
Diet: Although there is a great deal of interest in the relationship between diet and cancer, it remains uncertain whether and how diet affects the risk of ovarian cancer. Nevertheless, women are advised to follow general recommendations for a healthy diet: eat a diet that’s rich in whole grains, fruits, and vegetables; limit intake of red or processed meat; limit alcohol intake to one drink per day; and choose foods that help you maintain a healthy weight.11
Exercise: As is the case for diet, the relationship between exercise and ovarian cancer remains uncertain. But regardless of whether it reduces the risk of ovarian cancer, exercise provides many other important health benefits, such as a reduced risk of heart disease and colon cancer. Your doctor can help you find an exercise program that’s right for you. Current recommendations suggest at least 30 minutes of moderate to vigorous physical activity on five or more days per week.12
Screening and Early Detection of Ovarian Cancer
For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the routine use of certain examinations or tests in persons who do not have any symptoms of a cancer in order to try to diagnose a developing cancer at the earliest possible stage. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.
The predictive value of screening may be greater for women who are at a high risk of developing ovarian cancer, but whether screening will allow for early detection and improve survival among such women remains unknown.
Annual Pelvic Examination: Currently, the most widely utilized way to detect ovarian cancer is to undergo a complete gynecologic examination at least once per year. Because ovarian cancers begin deep in the pelvis, they often do not cause any symptoms until they are at an advanced stage. In order to improve outcomes for women with ovarian cancer, the disease has to be diagnosed early, before it spreads.
Pay Attention to Symptoms: According to a consensus statement developed by the American Cancer Society, the Gynecologic Cancer Foundation, and the Society of Gynecologic Oncologists, certain symptoms are more likely to occur in women with ovarian cancer than women in the general population:
- Pelvic or abdominal pain
- Difficulty eating or feeling full quickly
- Urinary symptoms (urgency or frequency)
Women who experience these symptoms almost daily for more than a few weeks are encouraged to see a doctor, preferably a gynecologist.13
Transvaginal ultrasound plus CA-125 testing: For women who have a BRCA1 or BRCA2 mutation, ovarian cancer screening using a combination of transvaginal ultrasound and serum CA-125 testing may be recommended, even in the absence of firm evidence that it reduces ovarian cancer mortality.(14) Women with a BRCA1 or BRCA2 mutation are advised to talk with their physician about the optimal approach to risk reduction or surveillance.
Strategies to Improve Screening and Early Detection
Potential approaches to screening for ovarian cancer include transvaginal ultrasound and measurement of serum CA-125 levels, but thus far there is no firm evidence that these tests reduce ovarian cancer mortality. To improve upon currently available tests, researchers are exploring new approaches to early detection, such as combining several different blood tests, or using a combination of blood test and symptom results.15,16
- American Cancer Society. Cancer Facts & Figures 2017.
- Chobanian N, Dietrich CS. Ovarian Cancer. Surgical Clinics of North America. 2008; 88:285-99, vi.
- Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR, Clegg L, Eisner MP, Reichman M, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2005, National Cancer Institute. Bethesda, MD, , based on November 2007 SEER data submission, posted to the SEER web site.
- Armstrong, D. Ovaries and fallopian tubes. In: Abeloff MD ed. Abeloff’s Clinical Oncology, 4thPhiladelphia: Churchill Livingstone, 2008: 1827-50.
- Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in the Million Women Study. The Lancet. 2007;369:1703-10.
- Lacey JV, Brinton LA, Leitzmann MF et al. Menopausal Hormone Therapy and Ovarian Cancer Risk in the National Institutes of Health-AARP Diet and Health Study Cohort. Journal of the National Cancer Institute. 2006;98:1397-405.
- Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM. Does smoking increase the risk of ovarian cancer? A systematic review. Gynecologic Oncology. 2006;103:1122-9.
- Rebbeck TR, Lynch HT, Neuhausen SL et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2mutations. N Engl J Med. 2002;346:1616-1622.
- Hogg R, Friedlander M. Biology of epithelial ovarian cancer: implications for screening women at high genetic risk. J Clin Oncol. 2004; 22:1315-1327.
- Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303-314.
- Kushi LH, Byers T, Doyle C et al. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity. CA Cancer J Clin 2006 56: 254-281.
- American Cancer Society. Ovarian cancer has early symptoms. First national consensus on common warning signs. Available at: cancer.org/docroot/NWS/content/NWS_1_1x_Ovarian_Cancer_Symptoms_The_Silence_Is_Broken.asp.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology.™ Genetic/Familial High-Risk Assessment: Breast and Ovarian. V.1.2008. © National Comprehensive Cancer Network, Inc. 2008. NCCN® and NATIONAL COMPREHENSIVE CANCER NETWORK® are registered trademarks of National Comprehensive Cancer Network, Inc.
- Visintin I, Feng Z, Longton G, et al. Diagnostic markers for early detection of ovarian cancer. Clinical Cancer Research [early online publication] February 7, 2008. DOI: 10.1158/1078-0432.
- Andersen M, Goff B, Lowe K, et al. Combining a symptoms index with CA 125 to improve detection of ovarian cancer. Cancer [early online publication]. June 2008. DOI: 10.1002/cncr.23577.