Ovarian Cancer

September 20, 2011

Fluorescent Stained ovarian carcinoma cells

Ovarian cancer refers to a heterogeneous (diverse) group of diseases. The most common form of ovarian cancer, the epithelial ovarian cancers, tends to occur in women after the age of 50. This type of ovarian cancer was highly publicized with the diagnosis and death of actress and comedienne, Gilda Radner. it is this form of cancer that most individuals think of when they hear the term “ovarian cancer.” There are, however, two other forms of ovarian cancer: the germ-cell tumors and the stromal tumors.

The germ-cell tumors that are responsible for only 2-3% of ovarian cancers are identical to the tumors that cause testicular cancer in young men. Germ-cell tumors arise from the portion of the ovary that gives rise to the oocyte or “egg.” They tend to be diagnosed in the late teens and early 20s, they tend to involve only one gonad (sex gland) thus removal of the gonad (castration) is not required, and they are highly curable with chemotherapy. The stromal tumors that account for only 7% of all ovarian cancers arise from the portion of the ovary that produces hormones. These tumors can occur at any point of the life cycle. Because of their tendency for hormone production, these tumors can cause early puberty as well as masculinization. Like germ-cell tumors, ovarian stromal cancers tend to be diagnosed before they have spread and are associated with a favorable prognosis.

Epithelial ovarian cancer, which is by far the most common form of ovarian cancer, arises from either the surface of the ovary or from embryologic tissue (rests) within the ovary. There is no analogous (similar) tumor seen in men. The remainder of this section will focus on epithelial ovarian cancer.

While epithelial ovarian cancer is not the most common of the gynecologic cancers, it is responsible for more deaths than uterine and cervical cancer combined. For this reason, ovarian cancer is one of the most dreaded of the female cancers. The primary reason for the high mortality rates seen with epithelial ovarian cancer is the fact that this disease is usually discovered only after it has spread well beyond the ovary (only 25% of cases have not spread beyond the ovary at the time of diagnosis). When epithelial ovarian cancer is diagnosed in the early stage (i.e., still limited to the ovary), the likelihood of cure is actually quite high (approximately 70-90% cure rate). Unfortunately, once the disease has spread outside of the pelvis, the cure rates are low (less than 20% likelihood of cure).

The reason for later diagnosis of epithelial ovarian cancer is that this disease tends not to cause symptoms in its early stages. The female pelvis is built to carry a pregnancy, thus there is an ingrained tolerance for the presence of a “mass” in the pelvis. The early symptoms are often nondescript. A vague sense of bloating or abdominal discomfort and indigestion are the more commonly reported symptoms of ovarian cancer. These symptoms are common in the general population and usually do not represent the presence of a malignancy. However, if any such symptom is progressively worsening or significant enough that the physician feels a diagnostic evaluation should be undertaken, it is wise to include a pelvic ultrasound in the evaluation, even if the symptoms are more in the abdomen than the pelvis. It is not at all infrequent for a patient, who ultimately turned out to have ovarian cancer, to have undergone an extensive gastrointestinal evaluation with specialized evaluation of the colon (colonoscopy) and stomach (gastroscopy)—both of which tend to be negative in women with ovarian cancer. Often neither specialized imaging techniques (computed tomography [CT] scan) of the abdomen and pelvis nor pelvic ultrasound (both of which would likely have made the diagnosis) are performed until a much later date, when symptoms are extreme.

SCREENING

Because of high cure rates when discovered early and because at present most cases are diagnosed late, ovarian cancer is an excellent candidate for using a screening test. Unfortunately, development of a highly effective screening methodology has been difficult. There is a general misconception that measurement of a specific compound found to be abnormal in ovarian cancer (serum CA-125) should be performed on all women to screen for ovarian cancer. While a rise in CA-125 is associated with ovarian cancer, a large body of data has shown that in most cases, elevation of CA-125 is due to a cause other than ovarian cancer in the general population. For this reason, CA-125 measurement alone is not an effective screening tool, as most abnormal readings will not be due to ovarian cancer and will thus lead to unnecessary anxiety and the performance of unnecessary diagnostic evaluations and surgical treatments.

Pelvic ultrasound performed with a vaginal probe has also been investigated as a screening tool. While it has been shown to detect the presence of asymptomatic ovarian cancers, its usefulness is limited by the fact that the “false positive rate” (the percentage of women who have an abnormal ultrasound who turn out not to have ovarian cancer) is high, perhaps as high as 80%. Many of the cancers detected by ultrasound screening are of the better prognostic variety (and would have likely remained localized to the ovary even if the diagnosis had been made without screening). Some cancers, mostly those that carry a poor prognosis, are missed by ultrasound screening. The British have conducted a study on approximately 20,000 women using pelvic ultrasound in conjunction with CA-125. They found that women diagnosed with ovarian cancer while undergoing screening lived longer than women with ovarian cancer who were not screened. However, a significant difference in long-term survival was not detected, though there appeared to be a trend toward lower mortality in the screened group. A much larger study is presently under way, which will hopefully definitively answer the question regarding the use of a combined serum CA-125 and ultrasound as a valuable screening tool. It is important to note that these studies are generally performed on postmenopausal women because they are far less likely than premenopausal women to have false-positive CA-125 or ultrasound readings.

At present, screening is offered to women at markedly increased risk of ovarian cancer because they carry a genetic mutation associated with a high likelihood of development of ovarian cancer. For the general population, ovarian cancer screening has not so far been proven to be beneficial in reducing the mortality from this disease. Modalities other than CA-125 and ultrasound, such as serum proteomics (a technique whereby serum is “fingerprinted” to identify its protein signature to look for patterns highly suggestive of ovarian cancer), are under investigation and show promise.

TREATMENT

If a woman is suspected to have ovarian cancer on the basis of her diagnostic evaluation, referral to a gynecologic oncologist is necessary. This specialist who is highly trained in the management of ovarian cancer will optimize both the surgical and chemotherapeutic management of the patient. It is extremely important that the initial surgery be performed in a fashion that can optimize chances for survival. In women with apparently early tumors, it is key that a complete “staging” procedure be done to look for hidden sites of disease that are not obvious to the naked eye. This involves biopsies at multiple sites of the intra-abdominal lining and of strategic lymph nodes. Microscopic metastases (clusters of tumor cells that have spread to other parts of the body) to these structures have been reported to occur in up to 30% of individuals whose disease appears limited to the ovary. Detection of such metastases would lead to a different, more aggressive, treatment plan. For women with disease that has already metastasized, the goal of the initial surgery is to remove as much of the disease as possible, because the amount of disease remaining at the end of surgery has consistently been shown to affect outcome. This surgery can be extremely challenging and requires both the technical skill and judgment that come with experience from treating ovarian cancer. It has been shown that the outcome of the initial surgery is clearly improved when a gynecologic oncologist is involved, as compared to a general gynecologist or a general surgeon. In some cases, it may be advisable to delay the surgery and use chemotherapy first to contain the disease because the patient is so weakened by the cancer that a large surgery is too risky.

Once a diagnosis has been made, chemotherapy is usually, but not always, necessary. The initial chemotherapeutic approach involves the use of two agents, called carboplatin and paclitaxel. These agents are usually given in an outpatient setting over approximately 5-6 hr. Generally 3-6 courses of chemotherapy are given (depending on how advanced the initial disease was), 3 weeks apart. After chemotherapy is complete, some women who had advanced disease may benefit from a second operation referred to as second-look, to try to ascertain whether the disease is no longer evident. Frequently, after the initial six cycles of chemotherapy, consolidation chemotherapy with paclitaxel alone is recommended for women who initially had advanced disease, to try to optimize outcome. While the majority of women respond well to chemotherapy eventual relapses are common. There are a variety of agents available to treat women with recurrent ovarian cancer, but cure after recurrence is extremely rare. The goal of treatment in the recurrent situation is to lengthen life (and hopefully preserve quality of life) for as long as possible.

SEE ALSO: Cancer, Hysterectomy

Tags: , ,

Category: O