Ovarian Cancer – Causes, Complications, and Treatment.

Definition

The term “ovarian cancer” includes several different types of cancer that all arise from cells of the ovary. Most commonly, tumors arise from the epithelium, or lining cells, of the ovary. These include epithelial ovarian (from the cells on the surface of the ovary), fallopian tube, and primary peritoneal (the lining inside the abdomen that coats many abdominal structures) cancer. These are all considered to be one disease process. There is also an entity called ovarian low malignant potential tumor; these tumors have some of the microscopic features of a cancer, but tend not to spread like typical cancers.

 

Epidemiology

Internationally, the incidence ranges from 3.1 cases per 100,000 women in Japan to 21 cases per 100,000 women in Sweden. Around the world, more than 200,000 women are estimated to develop ovarian cancer every year and about 100,000 die from the disease.

Epithelial ovarian cancer occurs most commonly in white women in the industrialized countries of northern and western Europe and North America and least commonly in India and Asia. Asian women have low risk unless they relocate to North America or Europe. Scandinavian and Norwegian women have the highest risk.

Types of ovarian cancer

There are many types of ovarian cancer. Some types of ovarian cancer are extremely rare and require specialized treatment.

The main types, which are listed below, are named for the cells where they start.

Epithelial ovarian cancer: About 90% of ovarian cancers start in the epithelium tissue, which is the lining on the outside of the ovary. This type of ovarian cancer is divided into serous, mucinous, endometrioid, clear cell, transitional and undifferentiated types. The risk of epithelial ovarian cancer increases with age, especially after the age of 50.

Germ cell ovarian cancer: Germ cell tumors account for about 5% of ovarian cancers. They begin in the egg-producing cells. This type of ovarian cancer can occur in women of any age, but about 80% are found in women under the age of 30. The main subtypes are teratoma, dysgerminoma, endodermal sinus tumor and choriocarcinoma.

Stromal ovarian cancer: These tumors, about 5% of ovarian cancers, grow in the connective tissue that holds the ovary together and makes estrogen and progesterone. Most are found in older women, but sometimes they occur in girls. Stromal tumors usually do not spread as fast as other ovarian tumors. Sub-types include granulosa, granulosa-theca and Sertoli-Leydig cell tumors.

Primary peritoneal ovarian cancer: It is a rare cancer. It has cells like those on the outside of the ovaries, but it starts in the lining of the pelvis and abdomen. Women can get this type of cancer even after their ovaries have been removed. Symptoms and treatment are similar to epithelial ovarian cancer. Fallopian tube cancer is also a rare cancer. It starts in the fallopian tube and acts like epithelial ovarian cancer. Symptoms and treatment are similar to ovarian cancer.

Risk factors of ovarian cancer

The causes of ovarian cancer are unknown, but the risk factors include:

Age: Ovarian cancer is most common in women over 50 and in women who have stopped menstruating (have been through menopause), and the risk increases with age

Reproductive history: Women who have not had children, were unable to have children, or had children over the age of 30 may be slightly more at risk

Having endometriosis: A benign (non-cancerous) condition in which the tissue that lines the uterus (endometrium) is also found in other areas of the body

Lifestyle factors: Such as being overweight or eating a high-fat diet

Hormonal factors: Including early puberty or late menopause, or using oestrogen-only hormone replacement therapy (HRT) for five years or more.

Some factors may reduce the risk of developing ovarian cancer. These include having children, breastfeeding, using the combined oral contraceptive pill for several years, and having your fallopian tubes tied (tubal ligation).

Causes of ovarian cancer

It’s not clear what causes ovarian cancer. In general, cancer begins when a genetic mutation turns normal cells into abnormal cancer cells. Cancer cells quickly multiply, forming a mass (tumor). They can invade nearby tissues and break off from an initial tumor to spread elsewhere in the body (metastasize).

Symptoms

Symptoms of ovarian cancer:

• Bloating
• Pelvic or abdominal pain
• Trouble eating or feeling full quickly
• Feeling the need to urinate urgently or often

Other symptoms of ovarian cancer can include:

• Fatigue
• Upset stomach or heartburn
• Back pain
• Pain during sex
• Constipation or menstrual changes

If symptoms are new and persist for more than two weeks, it is recommended that a woman see her doctor, and a gynecologic oncologist before surgery if cancer is suspected.

Diagnosis and test

Your doctor may suspect you have ovarian cancer after taking your medical history and doing a physical examination. To confirm the diagnosis, your doctor will arrange special tests. These tests may also be used to “stage” and “grade” the cancer and to help plan treatment. Your doctor will do one or more of the following tests to make a diagnosis.

Physical examination: A physical examination allows the doctor to look for any signs of ovarian cancer. During a physical examination, the doctor may do a pelvic (gynecological) examination to feel the uterus and ovaries and look at the vagina and cervix. Your doctor may also do an abdominal examination to feel for lumps or enlargement of organs such as the liver.

Imaging studies: Imaging studies allow tissues, organs and bones to be looked at in more detail. Using x-rays, ultrasounds, CT scans, MRIs or bone scans, your healthcare team can get a picture of the size of the tumour and see if it has spread. These tests are usually painless and do not require an anesthetic.

A transvaginal ultrasound may be done to diagnose ovarian cancer. A transvaginal ultrasound uses sound waves to form a picture of the vagina, uterus, Fallopian tubes and ovaries. A small probe is inserted into the vagina to look for dark or dense areas on the image that may be cancer.

Blood tests: Blood is taken and studied to see if the different types of blood cells are normal in number and appearance. The results show how well your organs are working and may suggest whether you have cancer and if it has spread. The blood may also be tested for body chemicals called tumour markers. For ovarian cancer, the blood may be tested for several tumour markers, including CA-125. CA-125 is a substance found in ovarian cancer cells and in some normal tissues. If the CA-125 level is high, there is a higher chance of ovarian cancer and some other conditions. CA-125 can also help tell whether the cancer has spread or not.

Biopsy: A biopsy is usually necessary to make a definite diagnosis of cancer. Cells are removed from the body and checked under a microscope. If the cells are cancerous, they may be studied further to see how fast they are growing and how different they look from normal cells. There are different ways to do a biopsy

For ovarian cancer, your doctor may choose to examine and take samples of tissue or fluid from the abdomen. This may be done by laparoscopy or laparotomy.

• For a laparoscopy, a thin, flexible tube with a light and camera at the end is inserted through a small cut near the belly button. Your doctor can look around the abdomen and pelvis and take several small biopsy samples. A local anesthetic (freezing) is used to numb the area.
• A laparotomy is an operation used to diagnose and treat ovarian cancer. If cancer is found during the operation, your doctor will remove as much of the cancer as possible. A laparotomy is done through an incision in the abdomen under a general anesthetic (you will be unconscious). You may stay in the hospital for several days after the surgery.

 Staging and grading

Once a definite diagnosis of cancer has been made, the cancer is given a stage and a grade. This information helps you and your healthcare team choose the best treatment for you. The cancer stage describes the tumour size and tells whether it has spread. For ovarian cancer, there are 4 stages.

Stage	Description
1	Cancer is found in one or both ovaries. The cancer cells may be on the surface of the ovaries or in fluid collected from the abdomen.
2	Cancer has spread to other tissues in the pelvis. Cancer cells may be in fluid collected from the abdomen.
3	Cancer has spread to tissues outside the pelvis to organs of the abdomen or to nearby lymph nodes.
4	Cancer has spread outside the pelvis and the abdomen to distant parts of the body.

Stages of ovarian cancer

A grade is given based on how the cancer cells look and behave compared with normal cells. This can give your healthcare team an idea of how quickly the cancer may be growing. To find out the grade of a tumour, the biopsy sample is examined under a microscope. There are 3 grades as follows

Grade	Description
1	Low grade – slow-growing, less likely to spread
2	Moderate grade
3	High grade – tend to grow quickly, more likely to spread

 Complications

• Complications of the tumour: torsion, rupture, infection.
• Complications of treatment: bone marrow depression, infection, neurotoxicity, nephrotoxicity, ototoxicity.
• Complications of advanced disease: malnutrition, electrolyte imbalance, small and large bowel obstruction, infection, ascites, pleural effusion.

Treatment and medications

Treatment options vary depending on the stage of the cancer, and are assessed taking into account the following variables:

• Tumour size
• Tumour position
• Degree of spread
• Patient’s physical condition

Until recently treatment options for ovarian cancer were limited to surgery and chemotherapy. However in 2011, the European Commission (EC) announced the approval of a biological therapy in combination with standard chemotherapy (carboplatin and paclitaxel) as initial treatment for advanced (stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. This marked the first new effective treatment option for women with advanced ovarian cancer in 15 years. Radiotherapy is not frequently used to treat ovarian cancer.

Surgery

Surgery is used to remove as much of the tumour as possible. This is known as debulking surgery or cytoreduction. Patients most commonly have both ovaries removed (bilateral oophorectomy) and a hysterectomy (removal of the uterus). In young women who wish to remain fertile, only the affected ovary is removed and the uterus is left in place. In patients diagnosed with early disease, surgery alone is usually sufficient but in advanced disease, debulking surgery followed by chemotherapy is recommended.

Chemotherapy

Chemotherapy after surgery is referred to as ‘front-line’ or ‘first-line’ treatment and involves a combination of a platinum and taxane-based chemotherapy (usually carboplatin and paclitaxel). Patients with advanced ovarian cancer who aren’t initially able to undergo surgery due to large ascites or invasive tumours can be treated with chemotherapy before being considered for surgery (neoadjuvant treatment).8 Ovarian cancer usually responds to chemotherapy but unfortunately, in the majority of cases the cancer returns (known as “relapse” or “recurrence”), resulting in half of patients eventually dying from the disease.2 When the cancer returns, the only currently available treatment option is further chemotherapy. The choice of chemotherapy at this stage depends on how quickly the cancer has returned.

Biological therapies

Biological therapies are a new approach to treating advanced ovarian cancer. They are typically given in combination with chemotherapy and represent the first new treatment option for women in many years.

Prevention of ovarian cancer

You cannot control some things that put you at risk, such as your family history or inheriting gene changes. But you can make some personal choices that lower your risk of cancer and other diseases.

• Eat a healthy diet with plenty of fruits, vegetables, and whole grains.
• Use of oral contraceptives, especially for more than 10 years
• Previous pregnancy
• History of breast-feeding
• Daily use of aspirin
• Be active. Talk with your doctor about what kinds of activity and how much activity would be good for you.