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Ovarian cancer is the ninth most common cancer in women, and the fifth leading cause of female cancer death. Detection of ovarian cancer while it is in its early stages significantly improves prognosis. Unfortunately, most cases of ovarian cancer are discovered when the cancer is already advanced.
Unlike Pap tests for cervical cancer, there is currently no effective screening method for ovarian cancer. Imaging tests such as transvaginal ultrasound and blood tests such as CA-125 have not proven to be useful screening tools. Studies indicate that screening with these tests does not reduce ovarian cancer death and may cause women to undergo unnecessary medical treatment due to their high rate of “false positives.”
The United States Preventive Services Task Force and other medical associations do not recommend routine screening for ovarian cancer for most women. However, these tests can help doctors track the results of treatments for ovarian cancer.
Ovarian cancer grows quickly and can progress from early to advanced stages within a year. Paying attention to symptoms can help improve a woman's chances of being diagnosed and treated promptly. If you have the following symptoms on a daily basis for more than a few weeks, you should see your doctor (preferably a gynecologist):
The main risk factors of ovarian cancer are:
Factors that may help reduce the risk of ovarian cancer include:
Ovarian cancer is usually treated by surgery followed by chemotherapy. Surgery involves removal of the ovaries, fallopian tubes, uterus, and the omentum (a layer of fatty tissue in the abdomen).
Patients with ovarian cancer should seek care from a qualified gynecologic oncologist (a surgical specialist in female reproductive cancers) and a qualified medical oncologist with special expertise in the chemotherapy of gynecologic cancer.
According to a 2013 study , only about a third of American women receive the proper care for ovarian cancer as outlined in guidelines by the National Comprehensive Cancer Network (NCC). Women whose care adhered to the NCCN guidelines had a much better chance for survival. The best outcomes were seen with hospitals and doctors that treated a large number of ovarian cancer patients.
The ovaries are two small, almond-shaped organs located on either side of the uterus. They are key components of a woman's reproductive system:
Ovarian cancers are potentially life-threatening malignancies that develop in one or both ovaries. Malignant ovarian tumors generally fall into three primary classes:
Epithelial Tumors. Epithelial tumors account for up to 90% of all ovarian cancers and are the primary focus of this report. These cancers develop in a layer of cube-shaped cells known as the germinal epithelium, which surrounds the outside of the ovaries.
Germ Cell Tumors. Germ cell tumors, which account for about 3% of all ovarian cancers, are found in the egg-maturation cells of the ovary. They occur most often in teenagers and young women. Although they progress rapidly, they are very responsive to treatments. About 90% of patients with germ cell malignancies can be cured, often preserving fertility.
Stromal Tumors. Stromal tumors, which account for about 6% of all ovarian cancers, develop from connective tissue cells that hold the ovary together and that produce the female hormones, estrogen and progesterone. Stromal tumors do not usually spread, in which case the prognosis is good. If they spread, however, they can be more difficult to treat than the other types of ovarian tumors.
Ovarian cancer progresses almost silently, usually with vague symptoms. By the time serious symptoms do appear, the ovarian tumor may have grown large enough to shed cancer cells throughout the abdomen. At such an advanced stage, the cancer is more difficult to cure.
Ovarian cancer cells that have spread outside the ovaries are referred to as metastatic ovarian cancers. Ovarian tumors tend to spread to the following locations:
Cancer cells can also spread to other organs through lymph channels and the bloodstream.
Not all ovarian growths are malignant. Benign ovarian cysts are common and are entirely different from ovarian cancer.
Ovarian cysts typically develop in one of two ways:
Both follicular cysts and corpus luteum cysts are normal parts of the menstrual cycle and nearly always resolve within one or two cycles without treatment.
Ovarian cancer is the ninth most common cancer in women, and the fifth leading cause of female cancer death. Each year in the United States, about 22,000 women are diagnosed with ovarian cancer. About 14,000 American women die each year from the disease.
Certain factors increase the risk for ovarian cancer, while other factors reduce risk. Many of the preventive factors are related to the number of times a woman ovulates during her lifetime, which is indicated by the number of menstrual periods she has. Fewer menstrual periods and ovulations appear to be associated with reduced risk for ovarian cancer.
The main risk factors for ovarian cancer are:
Age. Ovarian cancer risk increases with age. About two-thirds of women are diagnosed with ovarian cancer at age 55 or older. The average age for the onset of ovarian cancer is about age 63, although ovarian cancer can develop in women of all ages.
Family History. A family history of breast or ovarian cancer is one of the strongest risk factors for ovarian cancer. Women are also at high risk for ovarian cancer if they have a family history of a hereditary form of colorectal cancer.
In general, women are considered at high risk for ovarian cancer if they have:
When a woman describes her family history to her doctor, she should include the history of cancer in women on both the mother's and the father's side. Both are significant.
Genetic Mutations. The main genetic mutations associated with increased ovarian cancer risk are:
Obesity. Many studies have found an association between obesity and increased risk for ovarian cancer.
Hormone Replacement Therapy (HRT). Long-term use (more than 5 years) of hormone replacement therapy (HRT) may increase the risk of developing and dying from ovarian cancer. The risk seems to be particularly significant for women who take estrogen-only HRT. The risk is less clear for combination estrogen-progestin HRT. For women who take HRT, those who have a uterus (have not had a hysterectomy) are given combination HRT because progestin helps protect against the development of uterine cancer.
Menstrual and Reproductive History. Women are at increased risk for ovarian cancer if they began menstruating at an early age (before age 12), have not had any children, had their first child after age 30, or experienced early menopause (before age 50).
Endometriosis. Endometriosis may increase the risk for certain types of ovarian cancer. However, most women with endometriosis do not develop ovarian cancer. Endometriosis is a condition in which the cells that line the uterus grow in other areas of the body, such as the ovaries.
Risk Factors with Less Conclusive Evidence. Dietary fats have been studied as a possible risk factor for ovarian cancer. While some research reports an association between a high intake in animal fats and a greater risk, other studies have not found that dietary fat intake increases the risk for ovarian cancer.
Some older studies indicated that use of the fertility drug clomiphene (Clomid) could increase the risk for ovarian cancer. However, infertility itself is a risk factor for ovarian cancer, so it is not certain whether fertility drugs play an additional role in affecting risk. More recent studies suggest that fertility drugs do not increase ovarian cancer risk.
There is inconclusive evidence as to whether environmental factors increase the risk for ovarian cancer. Possible carcinogens studied include radiation exposure, talcum powder, and asbestos.
In general, factors or behaviors that limit stimulation of the ovaries or inhibit ovulation seem protective. These preventive factors include:
Oral Contraceptives. Birth control pills definitely reduce the risk of ovarian cancer. Studies suggest that routine use of birth control pills reduces a woman's risk of ovarian cancer by about 50% when compared to women who have never taken oral contraceptives. The longer a woman takes oral contraceptives the greater the protection and the longer protection lasts after stopping oral contraceptives. However, birth control pills are not safe or appropriate for all women.
Pregnancy and Childbirth. The more times a woman gives birth, the less likely she is to develop ovarian cancer. Breast-feeding for a year or more after giving birth may also decrease ovarian cancer risk.
Tubal Ligation and Hysterectomy. Tubal ligation, a method of sterilization that ties off the fallopian tubes, has been associated with a decreased risk for ovarian cancer when it is performed after a woman has completed childbearing. Similarly, hysterectomy, the surgical removal of the uterus, is also associated with decreased risk. However, these procedures should not be performed solely for ovarian cancer risk reduction.
Preventive Factors with Less Conclusive Evidence. Some studies, but not all, have suggested that tea consumption is associated with reduced risk of ovarian cancer.
Women with a strong family history of ovarian cancer may wish to discuss these preventive strategies with their doctors.
Genetic Counseling and Screening for BRCA Genes. The latest guidelines from the U.S. Preventive Services Task Force (USPSTF) recommend BRCA testing for women at high risk for ovarian cancer. The USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA1 or BRCA2 genetic mutations).
Screening with Ultrasound or Blood Tests. Screening high risk women is not recommended:
Evidence indicates that these screening tests do not help prevent ovarian cancer death. In addition, these tests produce a high level of “false positives,” meaning that women may be incorrectly subjected to unnecessary invasive tests for ovarian cancer.
Removal of Ovaries (Oophorectomy). Surgical removal of the ovaries, called oophorectomy, significantly reduces the risk for ovarian cancer. When it is used to specifically prevent ovarian cancer in high-risk women, the procedure is called a prophylactic oophorectomy. Prophylactic oophorectomy is approximately 95% protective against ovarian cancer and is recommended for women at high risk for ovarian cancer. These women generally have the BRCA1 or BRCA2 genetic mutation, or have two or more first-degree relatives who have had ovarian cancer.
Bilateral oophorectomy is the removal of both ovaries. Bilateral salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. Several recent studies indicate that salpingo-oophorectomy is very effective in reducing risk for ovarian cancer in women who carry the BRCA1 or BRCA2 mutation.
Even after oophorectomy, women in high-risk groups for ovarian cancer still have a risk for the development of cancer in the peritoneum (the thin membrane that lines the inside of the abdomen).
Premenopausal women should be aware that oophorectomy causes immediate menopause, which poses a risk for several health problems, including osteoporosis and heart disease. Estrogen replacement, given for a period of time, can help offset these problems but may cause problems of its own. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who naturally enter menopause.
Ovarian cancer used to be considered a "silent killer." Symptoms were thought to appear only when the cancer was in an advanced stage. Now, doctors believe that even early-stage ovarian cancer can produce symptoms.
See your doctor if you have the following symptoms on a daily basis for more than a few weeks:
Ovarian cancer grows quickly and can progress from early to advanced stages within a year. Paying attention to symptoms can help improve a woman's chances of being diagnosed and treated promptly. Detecting cancer while it is still in its earliest stages may help improve prognosis.
Be aware that these symptoms are very common in women who do not have cancer and are not specific for ovarian cancer. While prompt follow-up with your doctor is important when one or more of these are present, there are many other explanations for these symptoms besides ovarian cancer.
Other symptoms are also sometimes associated with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain during intercourse, constipation, and menstrual irregularities.
Based on the symptoms and physical examination, the doctor may order pelvic imaging tests or blood tests. If these tests reveal possible signs of cancer, patients should be referred to a gynecologic oncologist who specializes in female reproductive system cancers.
Up to 95% of women diagnosed with ovarian cancer will survive longer than 5 years if the cancer is treated before it has spread beyond the ovaries. Although doctors are working hard to develop ways to diagnose early ovarian cancer, there are currently no effective screening tests for early detection. Therefore, only about 25% of ovarian cancer cases are diagnosed at such early stages. It is possible to perform genetic screening to detect high-risk women, but this raises some complex issues.
Every woman should have a regular annual examination with her doctor that includes a pelvic exam.
A pelvic exam is performed in two ways. The doctor inserts two fingers into the vagina while feeling the abdomen with the other hand. The doctor also performs a bimanual rectovaginal exam, which involves the insertion of one finger into the vagina and another into the rectum.
Both exams enable the doctor to evaluate the size and shape of the ovaries. Enlarged ovaries and abdominal swelling can be signs of ovarian cancer. A mass felt during a pelvic exam often requires further evaluation by ultrasound and sometimes requires surgery to make a definitive diagnosis.
Many women are treated each year in the United States because of ovarian growths or lesions. Many more women find out about some ovarian abnormality during their annual gynecological exam. The vast majority of conditions are noncancerous. They include:
Once a growth is detected, the additional tests described below may help the doctor evaluate the risk for it being cancerous. If ovarian cancer has been diagnosed, these tests are also used to monitor how the cancer is progressing.
Ultrasound. Ultrasound is a noninvasive diagnostic tool that can evaluate tumors and masses discovered during the rectovaginal exam:
Other Imaging Techniques. Other imaging techniques are less common for the diagnosis or evaluation of suspected ovarian cancer but may help determine if cancer has spread to other parts of the body:
CA-125 Blood Test. CA-125 is a protein that is secreted by ovarian cancer cells and is elevated in over 80% of patients with ovarian cancer. Oncologists will usually only obtain a blood test for this protein if ovarian cancer is strongly suspected or has been diagnosed. In general, a CA-125 level is considered to be normal if it is less than 35 U/mL (microns per milliliter). The test may also be useful for evaluating tumor growth and predicting survival in patients with recurrent cancer who have been treated with topotecan or paclitaxel-carboplatin chemotherapy regimens.
The test is not useful for diagnosis or early screening, however. In about half of women with very early ovarian cancer, CA-125 levels are not elevated above the normal standard. Furthermore, an elevated level can be caused by a number of other conditions including:
OVA1 Blood Test. The OVA1 blood test helps predict whether ovarian cancer is more likely to be present in a pelvic mass. The test measures the level of CA-125 and four other proteins. The test can help doctors decide what type of surgery should be performed. The OVA1 test is used in addition to, not in place of, other diagnostic and clinical procedures. It is not used to screen for or provide a definite diagnosis of ovarian cancer, but can help doctors to determine that a malignancy is more likely to be present.
An exploratory surgical procedure is required to confirm a diagnosis of ovarian cancer. It is also necessary to properly stage a patient, since the imaging tests may miss small implants of ovarian tumor within the pelvis and the abdominal cavity. Surgery may be laparotomy or a less-invasive laparoscopy. A gynecologic oncologist usually performs these procedures.
Laparotomy is an open-surgery procedure that requires general anesthesia. The surgeon makes an incision from the pubic bone to the navel to explore the abdominal cavity. Laparoscopy does not require general anesthesia and the oncologist uses only small incisions to insert a lighted instrument to examine the organs and evaluate the spread of the tumor. With both procedures, tissue samples (biopsies) can be removed for further testing.
About 75% of women survive ovarian cancer at least 1 year after diagnosis. Nearly half are alive 5 years after diagnosis. This is called the 5-year survival rate.
Survival rates vary depending on different factors, including age and the stage at which it is detected. In general, women younger than age 65 have better survival rates than older women.
Unfortunately, most patients with ovarian cancer are not diagnosed until the disease is advanced. This usually means the cancer has spread to the upper abdomen. In order to establish a prognosis and determine treatment, the doctor needs to know the cell type, stage, and grade of the disease.
When examined under the microscope, there are a number of different cell types of ovarian cancer. Mucinous and clear cell tumors tend to be more difficult to treat.
Cancers are staged (I through IV) according to whether they are still localized (remaining in the ovary) or have spread beyond the original site.
The survival rate varies according to the cancer stage:
Tumors are graded according to how well or poorly organized they are (their differentiation). Ovarian tumors are graded on a scale of 1, 2, or 3. Grade 1 tends to closely resemble normal tissue and has a better prognosis than grade 3, which indicates very abnormal, poorly defined tissue.
In general, the course of treatment is determined by the stage of the cancer. Stages range from I to IV based on the cancer's specific characteristics, including whether it has spread beyond the ovaries. Surgery is the main treatment for ovarian cancer. Following surgery, women with higher-stage tumors may receive chemotherapy. Women can also consider enrolling in clinical trials that are investigating new types of treatments.
About 10 - 15% of epithelial ovarian tumors are referred to as "borderline" because their appearance and behavior under the microscope is between benign and malignant. These tumors are also called "carcinomas of low malignant potential" because they rarely metastasize or cause death. Borderline ovarian tumors are most often seen in younger women with epithelial ovarian cancer. Surgery is usually recommended to remove these tumors. Chemotherapy may also be used to treat borderline tumors that appear to have more aggressive features (such as recurring after surgery).
Stage I. In stage I, the cancer has not spread. It is confined to one ovary (stage IA) or both ovaries (stage IB). In stages IA and IB, the ovarian capsules are intact, and there are no tumors on the surface. Stage IC can affect one or both ovaries, but the tumors are on the surface, or the capsule (outer covering of the ovary) has burst, or there is evidence of tumor cells in abdominal fluid (ascites). The overall 5-year survival rate for stage IA or IB can be as high as 90%, depending on the type of tumors and whether cells are well or poorly differentiated. Stage IC has a poorer outlook than the earlier stages. It is very important that women receive an accurate staging assessment, including a pathologic review conducted by a gynecologic pathologist.
Stage II. In stage II, the cancer is in one or both ovaries and has spread to other areas in the pelvis. It may have advanced to the uterus or fallopian tubes (stage IIA), or other areas within the pelvis such as the bladder, colon or rectum (stage IIB), but is still limited to the pelvic area. Stage IIC includes the pelvic involvement described in stages IIA and IIB and also includes cancer cells found in the abdominal fluid.
Stage III. In stage III, one or both of the following are present: (1) The cancer has spread beyond the pelvis to the omentum (a layer of fatty tissue in the abdomen) and other areas within the abdomen, such as the surface of the liver or intestine. (2) The cancer has spread to the lymph nodes.
Stage IV. Stage IV is the most advanced cancer stage. The cancer may have spread to the inside of the liver or spleen. There may be distant spreading of the cancer, such as ovarian cancer cells in the fluid around the lungs.
Treatment options for stage I and stage II ovarian epithelial cancer may include:
Treatment options for stage III and stage IV ovarian epithelial cancer may include:
If ovarian cancer returns or persists after treatment, chemotherapy is the mainstay treatment, although it is not generally curative in the setting of relapsed disease. Clinical trial options include additional surgical debulking, targeted therapy with a biologic drug combined with chemotherapy, or hormone therapy.
Surgery for ovarian cancer uses laparotomy, a major abdominal operation. It is the primary diagnostic tool for ovarian cancer and also plays a role in treatment. Complete surgical intervention includes the following:
It is extremely important that patients with ovarian cancer seek care from a qualified gynecologic oncologist (a surgical specialist in female reproductive cancers) and a qualified medical oncologist with special expertise in the chemotherapeutic management of gynecologic cancer. Studies indicate that it is best for patients, especially those with advanced-stage ovarian cancer, to receive care at medical centers that specialize in cancer treatment and surgery.
Women of child-bearing age should discuss with their doctors any concerns and questions they may have about how various cancer treatments could affect their fertility. They may also wish to have a consultation with a fertility specialist. Assisted reproductive technology such as embryo or oocyte (egg) cryopreservation (“freezing”) may offer some women an option to later have children. It is very important that you have these discussions with your health care team prior to starting cancer treatment.
Surgical staging includes biopsies of the following:
An abdominal wash is performed by injecting a salt solution into the abdominal cavity to facilitate microscopic detection of cancerous cells not visible to the naked eye. The surgeon then evaluates the pelvis and abdomen and removes suspected cancer tissue. The entire affected ovary is usually removed (oophorectomy) during surgical staging if the surgeon believes it might be cancerous. The tissue is sent to a laboratory for an immediate evaluation called a frozen section diagnosis. The doctor will also examine the bowel and bladder for cancer invasion.
Debulking, also called surgical cytoreduction, involves removing as much of the tumor as possible. The goal is to leave behind no tumor larger than 1 centimeter. Debulking is usually followed by chemotherapy. Reducing the size of the tumor helps the chemotherapy act more effectively.
The surgery itself is typically performed as follows:
Hysterectomy results in infertility. A woman will no longer have menstrual periods and she can no longer become pregnant. Surgical removal of the ovaries (oophorectomy) causes immediate menopause. Symptoms such as hot flashes come on abruptly and may be more intense than those of natural menopause. Other menopausal symptoms include vaginal dryness, sleep problems, and weight gain. .
The most important complications that occur in women who have had their ovaries removed are due to estrogen loss, which places women at risk for osteoporosis (loss of bone density) and a possible increase in risks for heart disease. Hormone replacement therapy after a hysterectomy is given as estrogen-only therapy (ET). It does have risks, including increasing the chances for breast cancer and stroke. It does not appear to increase the risk for ovarian cancer recurrence.
The decision to use estrogen therapy (ET) depends in part on a woman's age as well as other medical factors. For younger women (in their 20s, 30s, or 40s), the benefits of ET for bone and heart health may outweigh the risks. For women closer to the age of menopause, risks may outweigh benefits. Discuss with your doctor whether hormone replacement therapy is a safe or appropriate option for you.
Bowel obstruction is common in ovarian cancer. Certain patients may need a surgical procedure called a colostomy when part of the colon is removed.
Following surgery, patients (other than those with early-stage, low-grade disease) usually have chemotherapy. Unlike surgery and radiation, which treat the cancerous tumor and the area surrounding it, drug therapy destroys rapidly dividing cells throughout the body, so it is a systemic therapy.
Ovarian cancers are very sensitive to chemotherapy and often respond well initially. Unfortunately, in most cases, ovarian cancer recurs. With treatment advances, however, more than half of women now survive 5 years or longer. Doctors are now approaching this disease as a chronic and potentially long-term illness that requires the following:
Standard Chemotherapy. The standard initial chemotherapy uses a combination of:
Chemotherapy for Relapsed or Refractory Cancer. Unfortunately, even in patients who respond, the disease eventually becomes resistant to the first-line drugs, and the cancer returns. Some ovarian tumors are resistant to platinum drugs.
Once cancer recurs or continues to progress, the patient may be treated with more cycles of carboplatin and a taxane drug, or a different type of chemotherapy drug may be used in combination treatment.
Recurrent ovarian cancer may be treated with gemcitabine (Gemzar, generic), a drug used in combination with carboplatin for women with advanced ovarian cancer that has relapsed at least 6 months after initial therapy. Other drugs used for recurrent ovarian cancer include doxorubicin (Adriamycin, Doxil, generic), etoposide (Vepesid, generic), and vinorelbine (Navelbine, generic).
Hormonal therapy is also an option for patients who cannot tolerate or who have not been helped by chemotherapy. Hormonal therapy drugs include tamoxifen (Nolvadex, generic), and aromatase inhibitors such as letrozole (Femara, generic), anastrozole (Arimidex, generic), and exemestane (Aromasin, generic).
In general, the typical initial chemotherapy regimen is:
Chemotherapy is either administered intravenously (by vein) or intraperitoneally (through the abdominal cavity). Recent research has indicated that patients with stage III ovarian cancer who receive intraperitoneal chemotherapy have a significant survival advantage compared with patients who receive standard intravenous chemotherapy. However, intraperitoneal chemotherapy can cause more severe side effects, including abdominal pain and bowel damage. Some patients cannot tolerate intraperitoneal chemotherapy. Intraperitoneal chemotherapy requires careful catheter insertion and maintenance, and doctors need to be well trained to perform this procedure.
Side effects occur with all chemotherapy drugs. They are more severe with higher doses and increase over the course of treatment. Some may be long-lasting.
Common side effects may include:
Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. These complications may include:
After surgery and chemotherapy, patients should have:
Any patient with ovarian cancer is a candidate for clinical trials. In addition to testing high-dose or combinations of chemotherapy, biologic drugs that target specific proteins are being investigated. These drugs are primarily being studied for treatment of advanced or recurrent ovarian cancer, in combination with standard chemotherapy drugs. The biologic drug bevacizumab (Avastin) has been the main targeted therapy studied for ovarian cancer.
Radiation therapy is not typically used in ovarian cancer. This is because radiation would need to be given to the entire abdomen and pelvis, increasing its toxicity. Radiation is sometimes useful to treat isolated areas of tumor that are causing pain and are no longer responsive to chemotherapy, and to kill cancer cells that still remain after other treatments.
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