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Cancer of the Ovary and Fallopian Tube

EPIDEMIOLOGY AND DIAGNOSIS

About 26,800 women are diagnosed with ovarian cancer each year in the United States. Of these women, approximately 14,200 will die of the disease. Ovarian cancer represents 55% of all deaths from gynecologic cancer. The risk of a woman developing ovarian cancer during her lifetime is 1-2%.

The etiology of ovarian cancer is not known, but risk factors include infertility, low parity, or both; use of talc on the perineum; high-fat diet; lactose intolerance; history of breast or colon cancer; and a family history of ovarian cancer. Smoking, alcohol use, coffee consumption, estrogen replacement therapy.

The 5-year survival rate for ovarian cancer by stage is not significantly different from the 5-year survival rate for other gynecologic cancers; however, there is a significant difference in stages, with ovarian cancer usually having spread into the abdomen in about two thirds of patients at the time of diagnosis. It is clear from these data that the single most important factor in the large number of deaths from ovarian cancer is the failure to diagnosis the disease at an early stage. The reasons for this failure correspond to the growth and spread patterns of the disease. Because the ovary floats freely in the pelvic cavity, a tumor can grow for some time without producing symptoms associated with involvement of, or pressure on, other organs.

SCREENING

One of the most significant ways to improve survival for patients with ovarian cancer would be to find a way to screen women for ovarian cancer and detect the disease before it spreads beyond the ovary. Currently available methods for screening for ovarian cancer are pelvic examination, serum CA 125 level.

STAGING AND DIAGNOSIS

Staging classification is made on the basis of surgical evaluation, and the removal of as much tumor as possible is the cornerstone of treatment. Despite the importance of surgery, some type of adjunctive treatment is almost always required. The proper surgical procedure and the appropriate choice of adjunctive therapy depend on the findings at initial exploration, the histologic type of the tumor, and the age.

Diagnosis

Unfortunately, most patients with ovarian cancer are diagnosed after the disease has spread beyond the ovary. In these patients, symptoms may be abdominal pain or a bloated feeling, gastrointestinal or urinary tract disturbances, or in many cases, the onset of clinically detectable ascites.

TABLE 7. Management Schema for a Patient with an Adnexal Mass

Observe and Repeat Examination in 4-6 Weeks Surgical Exploration

Reproductive age Premenarchal or postmenopausal*

Mass <8 cm Mass >8 cm

Simple cysts on ultrasonography Complex cysts on ultrasonography

Decreasing size Increase in size or persistence through 2-3 menstrual cycles

Cystic and smooth Solid and irregular

Mobile Fixed

Unilateral Bilateral

Asymptomatic Pain or other symptoms of acute intraabdominal process

EPITHELIAL CANCER

Treatment

Treatment of ovarian cancer usually involves several types of therapy. Surgical therapy is the initial form of intervention, but it is curative in only a small percentage of cases. Usually, adjunctive chemotherapy, radiation therapy, or both are necessary.

SURGICAL THERAPY

Surgical removal of epithelial cancer that is confined to the ovary, followed by a full surgical staging procedure, may be adequate therapy. In other early-stage patients, some type of adjunctive treatment may be required. Epithelial ovarian cancer is categorized as early disease (stages I and II with no residual cancer) and advanced disease (stage II with residual cancer and stage III and stage IV cancer).

Table 10 provides a classification system for patients within broad categories. Early ovarian cancer can be divided into low-risk and high-risk disease. For properly staged low-risk epithelial ovarian cancer.

CHEMOTHERAPY

Although surgery is an important aspect in the management of ovarian cancer, surgery alone is rarely curative and by itself will provide only brief palliation of advanced disease. Most patients with ovarian cancer require adjunctive chemotherapy. Fortunately, 75-80% of patients will respond to chemotherapy. Unfortunately, many patients develop resistance to chemotherapy before complete eradication of the cancer. For these patients, secondary or salvage chemotherapy is an important part of their treatment.

Primary Chemotherapy. In the 1960s, single alkylating agents were the chemotherapy of choice for epithelial ovarian cancer. The most commonly used drugs were melphalan and chlorambucil. Overall response rates were 45-55%, and complete clinical response was seen in 1520% of cases. In the 1970s, multidrug regimens resulted in an improvement in overall response rates as well as in complete clinical responses. The introduction of cisplatin in the late 1970s resulted in combination chemotherapy regimens that achieved overall response rates of 70-80% with complete clinical response rates of approximately 50%. The addition of cisplatin to multidrug regimen improves response rates and survival. Because of the ease of administration, most patients are treated with the combination of carboplatin and cyclophosphamide.

The Gynecologic Oncology Group recently reported the results of a randomized trial of cisplatin and paclitaxel in advanced epithelial ovarian cancer. In the trial, patients with stage III disease (tumors >1 cm) or stage IV disease received either cisplatin and cyclophosphamide or cisplatin and paclitaxel. There was a significant improvement in complete response rate, overall response rate, and disease-free survival for patients who received paclitaxel. Based on this study, the standard primary chemotherapy regimen for advanced ovarian cancer is cisplatin and paclitaxel. Several clinical trials are under way to define the best dose and duration of administration for paclitaxel. Other studies are evaluating the complications of carboplatin and paclitaxel.

Patients who are platinum resistant and have not received paclitaxel should be treated with systemic paclitaxel. Administration of paclitaxel has resulted in a 30-35% response rate as salvage therapy and a 25-30% response rate as salvage therapy in patients resistant to platinum therapy. Other drugs for which modest response rates have been reported are topotecan, ifosfamide, hexamethylmelamine, and low-dose oral etoposide (VP-16). All patients who require salvage therapy for epithelial ovarian cancer should be considered for clinical trials.

Radiation Therapy. The role of irradiation in the management of ovarian cancer remains controversial. There is little doubt that patients with early-stage ovarian cancer or microscopic residual advanced epithelial ovarian cancer can be cured with whole-abdominal radiation therapy.

The value of the serum CA 125 test in the follow-up of patients depends in large part on whether the patient had an elevated serum level before therapy, even though CA 125 levels do not always correlate with tumor volume. The serum test does, however, appear to be the best follow-up test available.

OVARIAN GERM CELL TUMORS

Malignant germ cell tumors of the ovary occur primarily in the second and third decades of life, although they are occasionally found in young girls and older women.

STROMAL TUMORS

Sex cord-stromal or sex cord-mesenchymal tumors include tumors of the female type (granulosa cell tumors and granulosa-theca cell tumors), the male type (Sertoli-Leydig tumors), and very rare types such as lipid cell tumors and gynandroblastoma. The majority of these rare tumors will never be seen by the practicing gynecologist.

The granulosa cell tumor is the most common malignant tumor of this group of neoplasms. As shown in Figure 4, these tumors occur throughout a woman's lifetime but are more common in the first four decades.

CANCER OF THE FALLOPIAN TUBE

The fallopian tube is the least common site of gynecologic cancer in females, accounting for fewer than 1,000 new cases each year. Histologically, these tumors resemble papillary serous carcinoma of the ovary in more than 90% of cases. Diagnostic criteria for primary fallopian tube carcinoma include the following:

The main tumor is in the tube and arises from the endosalpinx.

The pattern histologically reproduces the epithelium of the mucosa and usually