Ovarian cancer is not one disease, but many. The ovary is an organ that contains many different types of cells - the germ cells ("eggs"), the surface epithelial cells, the stromal cells that surround the germ cells, as well as blood vessels and other supporting tissues. Each of these cells has the potential to develop into a malignancy. The most common type of ovarian malignancies are the epithelial ovarian cancers, and of these, the most common is papillary serous carcinoma. All subsequent discussion will focus on these epithelial cancers.

Who gets ovarian cancer?
The simple answer is anybody. More specifically, post-menopausal women (about 51 years of age in the U.S.), women who have never been pregnant, women who have never used birth control pills (yes, oral contraceptives are protective), women who have a first- or second-degree relative with ovarian cancer, and women who have a personal or family history of breast or colon cancers are prone to this disease.

The very strongest risk factor is family history, but only 5% or 1 in 20 women with a cancer of the ovary will have one of the genetic variants. This means that, for most patients, there is nothing in their family tree to alert concern.

Symptoms
For years, many believed that there were no symptoms associated with ovarian cancers in their early stages. The truth of the matter is that the symptoms are so vague and non-specific that oftentimes both patients and doctors attribute them to other causes. Heartburn and early satiety (fullness after eating) are blamed on the spicy foods they had for dinner.

An increase in abdominal girth is middle-age spread and too many rich meals. The pain in the lower abdomen is a muscle pull from moving the lawn. Or frequent urination is a fallen bladder. It is of little surprise then, that three-quarters of patients with ovarian cancer have a metastatic, advanced stage of the disease when they are diagnosed.

Diagnosis
Diagnosis is made at surgery for most patients. Usually there is evidence on an ultrasound or CT scan of abnormalities in the ovaries. Oftentimes, there is free fluid or ascites present in the abdomen. Many times, a woman's pelvic examination is abnormal. CA-125 is a blood test that is often elevated in women with advanced-stage epithelial ovarian cancer (80%), though only half of the women with cancer confined to the ovary will have an elevation of this test. In post-menopausal women with evidence of a mass on examination, ultrasound or CT scan, a CA-125 can predict, with great accuracy, whether there is a cancer present.

Advances in Research/ Screening/Genetic Testing
With such a devastating disease that presents in advanced stages so often, research efforts have focused on ways of diagnosing the disease early through screening. Unfortunately, there is no screening test or combination of tests that has proven of benefit for the average patient. In women considered to be high risk, recent evidence suggests that screening transvaginal ultrasound may be of benefit. But, even in this carefully screened and evaluated group of patients, cancers eluded the investigators and were diagnosed within a year of their evaluation. In women who come from families where cancers of the breast, ovary, endometrium, and colon cluster, genetic testing can sometimes be of benefit. Testing requires a blood or tissue sample from the woman with the cancer to determine if a variant of the BRCA 1 or 2 gene exists, and if so, what it is. When this information is available, then the blood of other family members can be tested to determine if they carry the same abnormal gene. A mother has a 50% chance of transmitting the gene to her children (both boys and girls) and a 25% risk of transmitting it to her grandchildren. In some families where the expression of the gene is strong, women who carry the abnormal gene have a 40% lifetime risk of developing ovarian cancer. Many would recommend that such a woman foregoes imperfect screening tests and simply have her ovaries removed when her childbearing is completed.

Surgical Treatment
Once a mass has been identified and examined radiographically, surgery is necessary to make a complete diagnosis. Surgery provides the opportunity to define the disease and resect (surgically remove) it. When cancer is ostensibly confined to the ovary, a systematic exploration of the abdomen and pelvis with biopsies of some 15-20 different sites is performed (a staging laparotomy).

When, as is so often the case, the disease is scattered widely throughout the abdominal cavity, a resection of as much cancer as possible is performed, occasionally requiring the removal of portions of the intestine. Ovarian cancer has a characteristic spread pattern it sprinkles and studs the inside of the abdominal cavity, a "salt and pepper" effect. It is important for the operating surgeon to be aggressive in his or her approach to the management of this disease, since many studies have shown a correlation between the amount of residual cancer and the chances of a patient responding to chemotherapy and living longer. Those patients with the smallest amount of residual disease have the very best prognosis.

Prognosis
Prognosis is clearly related to several key features of a woman s cancer, most importantly stage and grade. Stage defines the extent of disease. For the overwhelming majority of women with ovarian cancer, the disease is advanced. Survival for Stage III or IV disease is 15-20% at five years. When fortunate enough to find the disease when it s confined to the ovary, survival for Stage I disease is 80-85%. Grade describes the pattern of growth as seen under the microscope. Grade 1 cancers have a pattern of growth similar to that of normal tissues, and these cancers grow more slowly and are more likely to do well. Grade 2 and 3 cancers have a very disordered pattern of growth and consequently, are more unpredictable in their behavior. The woman who has Stage 1 Grade 1 disease is likely to be cured by surgery alone.

Mainstay Treatment with Chemotherapy
After surgery, chemotherapy is the mainstay of treatment for ovarian cancer. A well-established standard therapy is a combination of paclitaxil (Taxol) and carboplatinum (Paraplatin), given intravenously every 3-4 weeks for 6 cycles. During this interval, CA-125 values should drop to normal quickly, usually within three months. The greatest value of CA-125 in patients with ovarian cancer is in the monitoring of response to therapy. Once therapy is completed, most patients enter a period of remission where physical examination, radiographs and even blood tests (including CA-125) are normal. This period usually last several months to years. CA-125 is often the first indication of recurrent disease, with elevations in this blood test typically occurring 5-6 months before any abnormalities on physical examination or X-ray.

When Cancer Recurs
When cancer recurs, or comes back, treatment options expand significantly. Gone are the days when we had little to offer these women. Topotecan, Doxil, Gemzar, Hycamptin, Vespid and Tamoxifen are just a few of the drugs in our arsenal. Unfortunately, though there are many choices, the chances of success begin to decline significantly. The chances of response to chemotherapy after the initial surgery approach 75-80%. Second-line agents all have response rates on the order of 15-25%, with none clearly superior to the others. Frequently, the most effective agents are the ones given initially, usually Taxol and Paraplatin. The longer the period of remission, the greater the likelihood of a second remission. Second remissions are usually shorter than the first, and almost invariably are followed by another recurrence. Surgery is occasionally of benefit, especially when the disease seems to be relatively limited in extent on a CT scan and the chances are great for removing all grossly evident (i.e., to the naked eye) tumor growths or when patients have signs and symptoms of intestinal obstruction (an inability to eat or drink without vomiting). Most patients lose their strength slowly over the course of several months and at the end, slip into a restful sleep.

Research into new drugs, approaches and technologies continues. The standard therapy for this disease has already changed in the last decade. As more information becomes available, we will hopefully make inroads in both the diagnosis and management of this disease.

Frequently Asked Questions

Question 1

I'm 45-years old, menstruating monthly and my best friend was just diagnosed with ovarian cancer. Her doctor suspected cancer because her CA-125 was elevated. Should I have this blood test performed?

Answer:
Probably not. There are many benign conditions that can cause elevations of CA-125 in young, menstruating women from pregnancy to fibroids, infection, adenomyosis, and endometriosis to name a few. This has not been shown to be an effective screening tool in any group of women, but it is least suited to patients such as this. Most gynecologists know this and will not recommend the test to their patients. A normal value may be reassuring, but an abnormal one can have devastating psychological consequences.

Question 2

I have been found to have a mass on my ovary, and my doctor wants to remove it laparoscopically. Is that okay?

Answer:
Many ovaries and ovarian cysts are removed through the laparoscope (so-called "band-aid" surgery). The decision about whether to make an incision or remove the mass through this other operation depends on several factors. Masses felt to carry a high likelihood of malignancy are usually removed through an incision. A vertical incision is indicated when both ovaries are involved, when the ovaries have both cystic, fluid-filled areas as well as solid areas, and when there is free fluid or ascites. When the likelihood of cancer is low, a laparoscopic approach may be indicated (usually the blood supply is ligated and cut, and the cyst is carefully punctured and pulled out through a small incision). The next major consideration is your surgeon's preference and experience. Many gynecologists do not perform laparoscopic surgery frequently. If in doubt, ask.

Question 3

My first surgery for my ovarian cancer was "suboptimal." What does that mean, and where do I go from here?

Answer:
A suboptimal tumor reduction means there was a significant amount of cancer left behind in the abdomen and pelvis. The definition varies from one source to the next, but nowadays, most investigators consider any operation where any remaining nodule of cancer is greater than 1-2 cms in diameter to be a suboptimal surgery. Data clearly indicates that these patients should receive three cycles of Taxol and Paraplatin chemotherapy followed by another surgical attempt to optimally reduce the tumor and then another three cycles of chemotherapy. Investigators in Europe clearly demonstrated a survival advantage to women treated with a second surgery when compared to women treated with chemotherapy alone.

Last Updated: February 1, 2001
Source: Geri-Lynn Fromm, MD
Texas Cancer Institute^®