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Cancer of the Ovary and Fallopian Tube

In 1999, approximately 26,800 women were diagnosed with ovarian cancer. Of these women, an estimated 14,200 will die of the disease, which represents 55% of all deaths from gynecologic cancer cancer of the ovary, cancer of the Fallopian tube, ovary cancer, Fallopian cancer, falopian tube, overy cancer. The risk of a woman developing ovarian cancer during her lifetime is 1-2%. The incidence varies with age and is 1.4 per 100,000 in women under age 40 years and 38 per 100,000 in women older than age 60 years. Figure 4 illustrates the prevalence of different types of ovarian cancer by

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, and viral infections (such as mumps) have not been associated with increased risk. Use of oral contraceptives, however, is protective for

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 and reproductive desires of the patient. There are few diseases encountered by the gynecologist that will demand as much knowledge and skill as the therapy of ovarian cancer.

Staging

The FIGO staging classification scheme for ovarian cancer is outlined in the box, page 42. The staging of advanced disease (spread throughout the abdomen) may be obvious to most physicians, but it is important for a surgeon to be meticulous in the staging of early ovarian cancer. In one study it 

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. Some patients with advanced disease have menstrual irregularity or postmenopausal bleeding, but these symptoms occur infrequently. Occasionally, a patient 

World Health Organization Classification of Ovarian Tumors

Epithelial Tumors Clear Cell (Mesonephroid) Tumors

Serous Tumors Benign

Benign Adenofibroma

Cystadenoma and papillary cystadenoma Of borderline malignancy (carcinomas of low malignant

Surface papilloma potential)

Adenofibroma and cystadenofibroma Malignant

Adenocarcinoma (carcinoma)

Of borderline malignancy (carcinoma of low malignant

potential) Transitional Cell Tumors

Cystadenoma and papillary cystadenoma Benign Brenner tumor

Surface papilloma Of borderline malignancy (proliferating)

Adenofibroma and cystadenofibroma Malignant Brenner tumor

Malignant Transitional cell carcinoma

Adenocarcinoma (papillary adenocarcinoma and Mixed Epithelial Tumors

papillary cystadenocarcinoma) Benign

Surface papillary carcinoma Of borderline malignancy

Malignant adenofibroma and cystadenofibroma Malignant

Mutinous Tumors Undifferentiated Carcinoma

Benign Unclassified Epithelial Tumors

Oystadenoma Germ Cell Tumors

Adenofibroma and cystadenofibroma

Dysgerminoma

Of borderline malignancy (carcinoma of low malignant

potential) Variant: with syncytiotrophoblast cells

Cystadenoma Yolk sac tumor (endodermal sinus tumor)

Adenofibroma and cystadenofibroma Variants: Polyvesicular vitelline tumor

Malignant Hepatoid

Adenocarcinoma and cystadenofibroma Glandular

Malignant adenofibroma and cystadenofibroma Variant: "Endometrioid"

Endometrioid Tumors Embryonal carcinoma

Polyembryona

Benign Choriocarcinoma

Adenoma and cystadenoma Teratomas

Adenofibroma and cystadenofibroma Immature

Of borderline malignancy (carcinoma of low malignant Mature

potential) Solid

Adenoma and cystadenoma Cystic (dermoid cyst)

Adenofibroma and cystadenofibroma With secondary tumor formation (specify type)

Malignant Fetiform (homunculus)

Adenocarcinoma Monodermal and highly specialized

Adenoacanthoma Struma ovarii

Adenosquamous carcinoma With thyroid tumor (specify type)

Malignant adenofibroma and cystadenofibroma Oarcinoid

Epithelial--stroma and stromal Insular

Adenosarcoma Trabecular

Stromal sarcoma Stromal carcinoid

Mesodermal (mOllerian) mixed tumors, homologous Mucinous carcinoid

and heterologous

Germ Cell Tumors, Teratomas (continued) Sex Cord-Stromal Tumors (continued)

Monodermal and highly specialized (continued) Sertoli-stromal cell tumors; androblastomas

Neuroectodermal tumors Well differentiated

Sebaceous tumors Sertoli cell tumor; tabular androblastoma

Others Sertoli-Leydig cell tumor

Mixed (specify types) (Leydig cell tumor)

Mixed (specify types) Of intermediate differentiation

Sex Cord-Stromal Tumors Variant

Granulosa-stromal cell tumors With heterologous elements (specify types)

Granulosa cell tumor Poorly differentiated (sarcomatoid)

Juvenile Variant

Adult With heterologous elements (specify types)

Retiform

Tumors in the thecoma-fibroma group

Mixed

Thecoma

Typical Sex cord tumor with annular tubules

Luteinized* Gynandroblastoma

Fibroma Steroid (lipid) cell tumors

Cellular fibroma Stromal luteoma

Fibrosarcoma Leydig cell tumor; hilus cell tumor (note: A rare Leydig

cell tumor is nonhilar)

Stromal tumor with minor sex cord elements Unclassified

Sclerosing stromal tumor

(Stromal luteoma)

Unclassified (fibrothecoma)

Others

Staging for Cancer of the Ovary

Staging of ovarian carcinoma is based on findings at clinical examination and by surgical exploration. The histologic findings are to be considered in the staging, as are the cytologic findings as far as effusions are concerned. It is desirable that a biopsy be taken from suspicious areas outside of the pelvis.

Stage I Growth is limited to the ovaries.

Stage IA Growth is limited to one ovary; no ascites present containing malignant cells. There is no tumor on the external surface; capsule is intact.

Stage IB Growth is limited to both ovaries; no ascites present containing malignant cells. There is no tumor on the external surfaces; capsules are intact.

Stage IC* Tumor is classified as either stage IA or IB but with tumor on the surface of one or both ovaries; or with ruptured

capsule(s); or with ascites containing malignant cells present or with positive peritoneal washings.

Stage II Growth involves one or both ovaries, with pelvic extension.

Stage IIA There is extension and/or metastases to the uterus and/or tubes.

Stage lib There is extension to other pelvic tissues.

Stage IIC* Tumor is either stage IIA or lib but with tumor on the surface of one or both ovaries; or with capsule(s) ruptured; or with ascites containing malignant cells present or with positive peritoneal washings.

Stage III Tumor involves one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or

inguinal nodes. Superficial liver metastasis equals stage III. Tumor is limited to the true pelvis but with histologically

proven malignant extension to small bowel or omentum.

Stage Ilia Tumor is grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces.

Stage IIIB Tumor involves one or both ovaries with histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; nodes are negative.

Stage IIIC There are abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes.

Stage IV Growth involves one or both ovaries, with distant metastases. If pleural effusion is present, there must be positive

cytologic findings to assign a case to stage IV. Parenchymal liver metastasis equals stage IV.

*To evaluate the impact on prognosis of the different criteria for assigning cases to stage IC or IIC, it would be of value to know whether the rupture of the capsule was spontaneous or caused by the surgeon and if the source of malignant cells detected was peritoneal washings or ascites.

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 reassessment after adjunctive therapy

is necessary for most patients with advanced disease. In a large percentage of patients, some type of salvage therapy is important. Table 10 outlines current therapies and therapeutic options for epithelial ovarian cancer.

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, survival is approximately 95% and no therapy has been shown to be more effective than

Primary Cytoreductive Surgery. Reports in the late 1960s indicated improved survival in patients who had extensive surgical resection followed by whole-abdomen radiation. In a 1975 study, the exact residual diameter of tumors was recorded, and size was related to duration of survival. All of the study patients had been treated postoperatively with a single alkylating agent. The study reported a survival time of 39 months for patients with no

*TAH indicates total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy. tSome investigators include grade 2 in the low-risk category. tUnilateral salpingo-oophorectomy permissible in patients who desire further childbearing. §Optimal (stage III, <1 cm residual).

Interval Cytoreductive Surgery. In 1989, a review of 1,777 cases reported in the literature found that the success rate for optimal cytoreduction was 33%. Thus, it is clear that a significant number of patients will begin initial adjunctive therapy with large-volume disease. Several investigators addressed this problem with the concept of interval cytoreductive surgery, in which patients receive a short course of chemotherapy and then undergo a second operation to remove residual tumor, followed by a continuation of chemotherapy. Results with this technique have been mixed, with some

Second-Look Laparotomy. The concept of second-look laparotomy in epithelial ovarian cancer was introduced in the 1960s, having been considered initially for gastrointestinal cancers in the 1940s and 1950s. Initially described by investigators at M. D. Anderson Hospital for patients with ovarian cancer treated with alkylating agents, the concept of second-look laparotomy was defined as the surgical evaluation of patients who were in complete clinical remission after primary chemotherapy. The purpose was to define a population of patients who were free of disease and would

Secondary Cytoreductive Surgery. Although there is wide acceptance of the concept of primary cytoreductive surgery, few publications have addressed the concept of secondary cytoreductive surgery. A review of the literature indicated that 32-74% of patients could have their disease

Palliative Surgery

Most patients who are not cured of ovarian cancer develop intestinal obstruction as the terminal event of their disease process. It appears that 50-75% of these patients can undergo some type of palliative resection or bypass surgery. These patients will survive 4-6 months with the ability to eat. The mortality of surgery is 12-30%, and the rate of developing serious complications is 15-49%.

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

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

Salvage Chemotherapy. About 15-20% of patients with advanced epithelial ovarian cancer will be "cured" by initial surgery and primary chemotherapy. Most patients, however (75-80%), either will have residual disease at the conclusion of initial therapy or will develop recurrent disease. For these patients, salvage therapy will be required. The most important issues to consider are the size and location of the persistent disease and

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. A review

Table 12. Long-term (5-10-year) Survival in Ovarian Carcinoma Patients Treated with Whole Abdominal Irradiation: Correlation of Survival with the Size of Tumor after Initial Surgery

Follow-Up Care

Patients with early-stage ovarian cancer usually have a low recurrence rate, providing they had full surgical staging and received appropriate therapy. Exceptions include patients with clear-cell cancers of the ovary. Because of the low recurrence rate, patients should be followed with a gynecologic examination and a serum CA 125 test every 3 months for the first year, every 4 months for the second year, and every 6 months for the next 3 years.

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. The tumors are usually accompanied by abdominal pain, and almost 10% of patients will present with an acute episode of torsion,

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

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 shows a 

The therapy of fallopian tube cancer is similar to the therapy of ovarian cancer; the most important initial therapy is effective cytoreductive surgery. As in ovarian cancer, residual disease is a good predictor of survival rates. The adjuvant therapy of choice is chemotherapy with platinum-based multidrug therapy, followed by a second-look laparotomy and second-line therapy as

There are no reports of the use of paclitaxel in fallopian tube cancer, hut one would surmise that this drug will have a significant role in the therapy of