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What is ovarian cancer?
Ovarian cancer is a malignant tumor that occurs in or near the ovaries. The term is also often used for closely related cancers that arise from the fallopian tubes or peritoneum, since these diseases can have similar biological properties, symptoms and treatment principles. In Sweden, around 700 new cases are diagnosed each year, and the disease is most common in postmenopausal women.
The most common form is epithelial ovarian cancer, which arises from cells on or near the surface of the ovary. There are also more unusual forms, such as germ cell tumors and granulosa cell tumors, which often occur in younger women and can produce other tumor markers in the blood.
Ovarian cancer can be difficult to detect early because the symptoms are often diffuse. Many stomach and pelvic complaints have much more common and harmless causes, but new and persistent symptoms should be evaluated medically.
Symptoms of ovarian cancer
Symptoms can vary and develop gradually over time. Due to the relatively nonspecific nature of the symptoms, investigations are difficult, especially the time from the first symptoms until the patient seeks care. It is primarily the combination of new symptoms and the fact that the complaints persist over time that may justify further investigation.
- increasing abdominal circumference or swollen stomach.
- feeling of pressure or discomfort in the lower abdomen.
- pain in the pelvis or abdomen.
- early feeling of satiety or decreased appetite.
- nausea or changed bowel habits.
- frequent urination.
- involuntary weight loss.
- fatigue and decreased general condition.
- shortness of breath in more advanced disease, for example if fluid collects in the pleura.
In more advanced disease, fluid can accumulate in the abdominal cavity, known as ascites, which can cause a significant increase in abdominal size, a feeling of heaviness and sometimes difficulty breathing.
Causes and risk factors for ovarian cancer
The exact cause of ovarian cancer is usually not possible to determine in an individual person. The disease occurs when cells in or around the ovaries undergo genetic changes that cause them to begin to divide uncontrollably and evade the body's normal control systems. Some changes occur during life, while others may be hereditary.
The risk is influenced by several factors, especially age, heredity, hormonal and reproductive history and certain gynecological conditions. Having a risk factor does not mean that you will develop ovarian cancer, and the disease can also occur without any known risk factors.
The risk of ovarian cancer increases with age and the disease is most common after menopause. This is partly due to the fact that genetic changes can accumulate in cells over time. More unusual forms of tumors, such as certain germ cell tumors, occur more often in younger women.
BRCA1 and BRCA2
Hereditary mutations in the genes BRCA1 and BRCA2 are among the most important known genetic risk factors for ovarian cancer. The genes have a central function in the cells' repair of DNA. When this repair ability is impaired, genetic damage can accumulate more easily and contribute to the development of cancer.
BRCA1 and BRCA2 are also linked to an increased risk of breast cancer, among other things. Therefore, the occurrence of both breast cancer and ovarian cancer in the same family may raise suspicion of hereditary cancer and justify genetic counseling and testing.
Heredity and family history
The risk is higher if a close biological relative, such as a mother, sister or daughter, has had ovarian cancer. The risk increases further if several relatives have been affected or if there is a combination of ovarian and breast cancer in the family. Only a small proportion of all ovarian cancer has a clearly hereditary background, but heredity is clinically important because it can affect both follow-up, preventive measures and choice of treatment.
In more advanced disease, fluid can accumulate in the abdominal cavity, known as ascites, which can cause a significant increase in abdominal size, a feeling of heaviness and sometimes difficulty breathing.
Causes and risk factors for ovarian cancer
The exact cause of ovarian cancer is usually not possible to determine in an individual person. The disease occurs when cells in or around the ovaries undergo genetic changes that cause them to begin to divide uncontrollably and evade the body's normal control systems. Some changes occur during life, while others may be hereditary.
The risk is influenced by several factors, especially age, heredity, hormonal and reproductive history and certain gynecological conditions. Having a risk factor does not mean that you will develop ovarian cancer, and the disease can also occur without any known risk factors.
The risk of ovarian cancer increases with age and the disease is most common after menopause. This is partly due to the fact that genetic changes can accumulate in cells over time. More unusual forms of tumors, such as certain germ cell tumors, occur more often in younger women.
BRCA1 and BRCA2
Hereditary mutations in the genes BRCA1 and BRCA2 are among the most important known genetic risk factors for ovarian cancer. The genes have a central function in the cells' repair of DNA. When this repair ability is impaired, genetic damage can accumulate more easily and contribute to the development of cancer.
BRCA1 and BRCA2 are also linked to an increased risk of breast cancer, among other things. Therefore, the occurrence of both breast cancer and ovarian cancer in the same family may raise suspicion of hereditary cancer and justify genetic counseling and testing.
Heredity and family history
The risk is higher if a close biological relative, such as a mother, sister or daughter, has had ovarian cancer. The risk increases further if several relatives have been affected or if there is a combination of ovarian and breast cancer in the family. Only a small proportion of all ovarian cancer has a clearly hereditary background, but heredity is clinically important because it can affect both follow-up, preventive measures and choice of treatment.
Lynch syndrome
Lynch syndrome is a hereditary condition caused by mutations in genes that normally repair errors that occur when DNA is copied. The condition is primarily known to increase the risk of colon cancer and endometrial cancer, but also entails an increased risk of ovarian cancer. In the case of a strong family history of, for example, colorectal cancer, endometrial cancer and ovarian cancer, genetic testing may therefore be relevant.
Endometriosis
Endometriosis is associated with a slightly increased risk of certain types of ovarian cancer, particularly clear cell and endometrioid ovarian cancer. The absolute risk for the individual is still low and the vast majority of women with endometriosis never develop ovarian cancer.
Ovulation and reproductive history
Factors that involve more ovulations during life have been linked to a slightly higher risk of ovarian cancer. One possible explanation is that each ovulation involves biological activity and tissue repair in the area around the ovary and fallopian tube, which over time may increase the possibility of genetic changes occurring.
Pregnancy and breastfeeding reduce the number of ovulations during life and are associated with a lower risk. Women who have not given birth have a statistically slightly higher risk compared to women who have had several full-term pregnancies.
Birth control pills and hormonal influence
The use of combined birth control pills is associated with a reduced risk of ovarian cancer. The protective effect increases with longer use and can persist for a long time after treatment has ended. Hormone replacement therapy after menopause, however, can affect the risk. In particular, longer treatment with estrogen alone has been linked to an increased risk of ovarian cancer. The individual benefit and risk of hormone therapy therefore always need to be assessed based on the entire medical situation.
Previous breast cancer
A previous breast cancer does not automatically mean that the risk of ovarian cancer is greatly increased. The association is particularly important when the breast cancer is part of a hereditary cancer syndrome, for example in the case of a mutation in BRCA1 or BRCA2. It is therefore family history, age at previous cancer diagnosis and genetic findings that determine whether a person has a clearly increased hereditary risk.
Factors that can reduce the risk of ovarian cancer
Several factors are associated with a lower risk of ovarian cancer, including:
- use of combined oral contraceptives.
- full-term pregnancies.
- breastfeeding.
- fewer ovulations during life.
- preventive surgery in people with a significantly increased hereditary risk.
In people with a documented mutation in, for example, BRCA1 or BRCA2, preventive removal of the fallopian tubes and ovaries may be relevant after completing family formation. This is a specialist medical measure that is assessed individually within genetic counseling and gynecological care. Ovarian cancer can also occur without known risk factors. Heredity is particularly important in certain tumor types and genetic testing may be necessary after diagnosis.
How is suspected ovarian cancer investigated?
The investigation is based on a combination of medical history, gynecological examination, imaging and blood tests. No single examination alone can determine whether a change in the ovary is cancer.
In cases of suspicion, a gynecological examination and vaginal ultrasound are usually performed as the first imaging diagnostic steps. If the findings or symptoms continue to raise suspicion, the investigation is supplemented with additional imaging and laboratory tests. In cases of well-founded suspicion, computed tomography of the abdomen and thorax is often used to assess the possible spread of the disease.
CA 125 in ovarian cancer
CA 125 is the most important blood-based tumor marker in cases of suspected epithelial ovarian cancer. CA 125 is a glycoprotein that can be released in increased amounts from certain gynecological tumors and from tissues lining the abdominal and thoracic cavities. An elevated CA 125 can occur in ovarian cancer, but the marker is not specific for cancer. Elevated levels can also be seen in, for example, endometriosis, menstruation, pregnancy, inflammation of the abdominal cavity and several other benign conditions.
A normal CA 125 does not rule out ovarian cancer either. In early disease, the value may be normal, and some tumor types do not produce CA 125 to any great extent. The analysis is therefore always used together with clinical findings and imaging diagnostics.
In already diagnosed epithelial ovarian cancer, CA 125 can also be used to monitor treatment and disease development. The care program states that CA 125 follows the course of the disease well in a large proportion of cases, but that there are exceptions, including in certain mucinous and clear cell tumors.
HE4 and other blood tests
When investigating suspected epithelial ovarian cancer, other laboratory tests may also be included. Regional cancer centers include CA 125, S-HE4, CEA and CA 19-9 in the preoperative investigation in cases of well-founded suspicion.
HE4 is a tumor marker that can provide complementary information together with CA 125. HE4 may be elevated in some epithelial ovarian tumors but, like CA 125, should not be used alone to diagnose cancer.
CEA and CA 19-9 may be relevant in some cases, especially when the appearance of the tumor or clinical picture raises suspicion of a mucinous tumor or if there is a need to distinguish a primary ovarian tumor from cancer that may originate in the gastrointestinal tract or other organs.
Blood tests for rarer forms of ovarian cancer
Not all ovarian tumors are epithelial. In younger women and when more unusual tumor types are suspected, other blood tests may be particularly relevant.
- AFP may be elevated in certain germ cell tumors, such as yolk sac tumors.
- hCG may be elevated in certain germ cell tumors.
- LD may provide additional information and may be elevated in dysgerminomas, among other things.
- Inhibin B may be elevated in granulosa cell tumors.
- AMH may, like inhibin B, be used in cases of suspected granulosa cell tumor.
- Calcium may be relevant in cases of suspected hypercalcemic small cell ovarian cancer.
In suspicion of non-epithelial ovarian cancer, a more targeted sampling is recommended based on age, the appearance of the tumor and the clinical question.
MRI of the pelvis in ovarian cancer
MRI of the pelvis provides detailed images of the ovaries, uterus, fallopian tubes and other structures in the pelvis. MRI has high tissue contrast and can be particularly valuable when a change in the ovary or adnex needs to be characterized more closely.
MRI can help to assess whether a change appears to be, for example, an endometrioma, teratoma, fibroma, myoma or a possible malignant tumor. The method has a good ability to distinguish many benign changes from suspected malignant adnexal changes, but cannot determine with certainty exactly what type of ovarian cancer it is.
When ovarian cancer is suspected, MRI is therefore often used as a complementary tool, especially when ultrasound does not provide sufficient information or when a change needs to be characterized in more detail. Computed tomography is often used to map possible spread to the abdomen, lymph nodes, liver or thorax.
Gynecological ultrasound and MRI complement each other
Gynecological ultrasound is usually the first-line method when a change in the ovaries is suspected. Ultrasound can show, among other things, size, shape, cystic and solid components and blood flow in a change.
MRI can then provide additional information about the composition of the tissue and the relationship to surrounding structures. The combination of gynecological examination, ultrasound, MRI if necessary and relevant tumor markers provides a more complete assessment than any single examination.
How is the diagnosis determined?
Blood tests and imaging can give a strong suspicion of ovarian cancer, but the definitive diagnosis is established through histopathological examination of tumor tissue. The tissue is analyzed to determine the type of tumor and how biologically aggressive it is.
In cases of suspected early operable ovarian cancer, the final tissue diagnosis is often made in connection with surgery. In cases of more advanced disease or clear signs of spread, tissue samples can be taken before treatment.
How is it assessed whether the cancer has spread?
Ovarian cancer often spreads within the abdominal cavity and can involve the peritoneum, lymph nodes and other organs. Therefore, the investigation does not only need to determine whether a tumor is present in the ovary, but also how widespread the disease is.
In cases of well-founded suspicion, contrast-enhanced computed tomography of the chest and abdomen is usually used to map tumor spread, intraperitoneal spread, liver metastases and possible spread outside the abdominal cavity. MRI may be an alternative or complement in certain situations.
Treatment of ovarian cancer
Treatment depends on the tumor type, stage, genetic characteristics and the patient's general condition. For epithelial ovarian cancer, treatment often consists of a combination of surgery and chemotherapy. Surgery aims to remove as much tumor tissue as possible. Cytostatics are often given after surgery and in some cases before surgery if the disease is more widespread.
For certain types of ovarian cancer, targeted drugs are also used, such as PARP inhibitors for tumors with certain genetic characteristics. Genetic analysis of the tumor and sometimes hereditary testing can therefore influence the choice of treatment.
Prognosis for ovarian cancer
The prognosis varies considerably depending on the type of tumor and how widespread the disease is at the time of diagnosis. Early disease that is limited to the ovary generally has a better prognosis than cancer that has spread to the abdominal cavity or to other organs. Because the symptoms can be diffuse, many cases are only discovered when the disease has become more widespread. It is therefore important to investigate persistent new symptoms from the abdomen and pelvis, especially when several symptoms occur at the same time.
When should you seek medical attention?
Contact your healthcare provider if you experience new symptoms such as a swollen stomach, persistent abdominal or pelvic pain, early satiety, unexplained weight loss, or changes in your urinary or bowel habits that do not go away.
These symptoms are in most cases due to causes other than ovarian cancer, but in cases of persistent symptoms, a gynecological examination, ultrasound, and blood tests such as CA 125 may be warranted as part of further investigation.
Important information about blood tests and screening
CA 125, HE4, and other tumor markers should not be used as stand-alone screening tests for ovarian cancer in people without symptoms or other risk factors. An elevated value does not automatically mean cancer, and normal values cannot reliably rule out the disease. If ovarian cancer is suspected, it is the combined assessment of symptoms, gynecological examination, imaging and laboratory tests that determine whether further investigation is needed.
