OVARIAN CANCER

William A. Peters, III, M.D.
Gynecologic Oncologist, Swedish Medical Center (Seattle, WA)

Introduction:

Approximately one in seventy women in the United States will develop ovarian cancer during their lifetime. The most common type of ovarian cancer is called “epithelial” ovarian cancer. The average age of a patient at the time of diagnosis is in their early sixties. There are rarer types of malignancies arising in the ovaries called germ-cell tumors and stromal tumors. These are very different in presentation and management and are more frequently seen in adolescent or young adults.

A subcategory of epithelial ovarian tumors is called “borderline tumors”. Another term for these is tumors of low malignant potential. Tumors that fall within this category have a very good prognosis even when they have spread beyond the ovary and are usually managed with surgery alone.

Risk Factors:

It has long been recognized that epithelial ovarian cancers are more common in families with a history of other female cancers particularly cancer of the ovary and cancer of the breast. It is now recognized that the majority of these families carry a mutation for one of two specific genes (BRCA 1 or BRCA 2). There is also a weaker association between the development of ovarian cancer and a family history of colon cancer. It is very important for a woman to discuss her family history with her physician and if appropriate receive genetic counseling.

Ovarian cancer is more common in women who have not been pregnant and is much less common in patients with multiple offspring. It has also been shown that the use of oral contraceptives (birth control pills) significantly reduces a woman’s risk of developing ovarian cancer. There have been some studies that suggested that the use of ovulation inducing drugs in infertility patients may increase their risk for development of ovarian cancer. This is difficult to sort out since infertility patients are at a higher risk for development of ovarian cancer just because of their low number of pregnancies and the observation of a higher risk in patients who receive fertility drugs may not be independent of this effect. It is known that there is a direct correlation between the number of times in a woman’s life that she ovulates, either spontaneously or with the use of fertility drugs, and the risk of developing ovarian cancer.

Screening:

Unfortunately there is not a proven screening modality for the early detection of ovarian cancer. A pelvic examination during an annual physical examination has been used as a screening method but it is not a very common way that an ovarian cancer is detected. A pelvic or transvaginal ultrasound can detect any abnormality in the ovary. Its use for screening however is complicated by the very large number of women who have completely benign cysts in their ovaries, many of which will go away with just follow-up examination performed one to three months later. A blood test called a CA-125 is a very reliable marker to follow a patient with ovarian cancer. Unfortunately however it is not a useful screening test for ovarian cancer. Many women have elevated CA-125s because of benign conditions such as endometriosis, uterine fibroids, or adenomyosis and the test is too non-specific for use as screening.

A large amount of research is being done around the world looking for an alternate blood test which might be specific enough to be used as a screening test. Likely such a test would first be utilized in high-risk patients (such as those with a strong family history) before it would be accepted for use in the general population.

DIAGNOSIS:

Except for the asymptomatic patient who has an early ovarian cancer discovered on pelvic examination or because of a x-ray done for another condition, the majority of patients diagnosed with ovarian cancer have disease that has spread beyond their ovaries. Symptoms commonly seen in these patients include indigestion, fullness after eating a small amount of food, loss of appetite, bloating, a sensation of pressure on the bladder or rectum, or an increase in their abdominal girth. These symptoms are non-specific and are also frequently seen in women with many other conditions such as irritable bowel syndrome, acid reflux, peptic ulcer disease, urinary tract infections, fibroids, and endometriosis. The diagnosis is most often suggested when a patient has an imaging study such as an ultrasound, a CAT scan, or an MRI. Ultimately the diagnosis is established with a surgical procedure.

TREATMENT:

Surgery remains the first and most critical step in the management of patients with ovarian cancer. It has been established that patients operated upon by a trained specialist in the management of gynecologic cancer (a Gynecologic Oncologist) and patients managed in institutions with higher volumes of ovarian cancer, have better long-term outcomes.

The majority of patients who prove to have ovarian cancer undergo a primary exploratory operation with removal of one or both ovaries. An intraoperative assessment by the pathologist (frozen section) will usually confirm the diagnosis. The patient then undergoes staging by the surgeon. This consists of a combination exploration and palpation of the contents of the abdominal cavity and biopsies. Patients with stage IA cancer have cancer limited to one ovary. Stage IB includes patients with involvement of both ovaries. Stage II patients have extension within the pelvis beyond the ovary. Stage III patients include those with involvement of the lymph nodes and/or involvement of the abdominal cavity. Stage IV patients have cancer that has spread outside the abdominal cavity or into the liver or spleen. Unfortunately, the majority of patients have stage III disease at the time of their initial presentation.

There is a very strong correlation between the extent to which the cancer can be removed and the prognosis. Removing cancer that has spread beyond the ovary is called debulking. In addition to removal of the uterus (hysterectomy) and the tubes and ovaries, debulking may involve removal of the omentum which is a fatty layer that hangs between the stomach and the colon and acts like the vacuum cleaner of the abdominal cavity. Sometimes tumor has to be removed from the surfaces within the abdominal cavity and sometimes debulking requires removal of portions of the intestinal tract or urinary tract.

The patients, whose tumor is removed (debulked) to less than 1 cm in maximum size, or especially if it can be removed to the point where it cannot even be seen or palpated, have the best long-term prognosis.

There will be some patients in whom the preoperative x-rays, physical examination, and overall assessment of their health indicates that they would not be a good candidate for primary surgery. In these patients an x-ray directed biopsy may be used to obtain a diagnosis. The patient may be offered primary chemotherapy and if they respond well to the chemotherapy, may undergo surgery at a later date. This is known as neoadjuvant chemotherapy and is appropriate for many patients.

Virtually all ovarian cancer patients except those with tumor limited to one ovary, will receive chemotherapy. Standard primary intervenous chemotherapy is usually given for approximately 4-6 months and employes a two drug regimen involving carboplatin and paclitaxel (Taxol). There have been suggestions that in some patients direct installation of the chemotherapy into the abdominal cavity (intraperitoneal or IP chemotherapy) may be more effective. This technique however requires more expertise and is associated with a higher complication rate and is not appropriate for all patients.

Approximately 85 percent of all patients who have advanced ovarian cancer will go into remission after receiving primary surgery and then chemotherapy. Even with advanced stage disease, some of these patients are still in remission many years later and may have been cured of their disease. In patients in whom the initial CA-125 was elevated, this test is a good marker. In these patients, a CA-125 will almost always rise before there is a recurrent tumor detectable by any other means.

Patients who do recur after primary chemotherapy will frequently have long survival with additional treatment which may involve additional surgery or chemotherapy. The longer the time interval from completion of first chemotherapy, the better the prognosis. There are a number of other chemotherapy drugs which have high activity in ovarian cancer and the decision of whether or not to go back and treat with carboplatin and Taxol or to use another drug will depend on multiple factors, especially the length of time the patient has been off of chemotherapy.

Over the past forty years, as both surgery and chemotherapy have rapidly improved, there has been a dramatic increase in the average length of survival in patients with ovarian cancer even without curing the majority of these patients.

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