Ovarian, Fallopian Tube, and Peritoneal Cancer

Etiology and Epidemiology

The cause of ovarian cancer is unknown. The patient characteristics found to be associated with an increased risk for epithelial ovarian cancer include white race; late age at menopause; family history of cancer of the ovary, breast, or bowel; and prolonged intervals of ovulation uninterrupted by pregnancy. There is an increased prevalence of ovarian cancer in nulliparous women and those who have been infertile.

The incidence of ovarian cancer varies in different geographic locations. Western countries, including the United States, have rates that are three to seven times higher than those in Japan. Second-generation Japanese immigrants to the United States have an incidence of ovarian cancer similar to that of American women. White Americans experience ovarian cancer about 1.5 times more frequently than do black Americans.

Approximately 10% of epithelial ovarian cancers occur in women with a hereditary predisposition. Although women with hereditary cancers may have two or more first-degree relatives on either the paternal or maternal side who have had breast or ovarian cancer, recent studies have shown that 30-40% of patients with a BRCA germline mutation have no family history of disease. It is recommended that all patients with a high-grade serous or endometrioid ovarian cancer be referred for genetic counseling and possible genetic testing. The pattern of inheritance is autosomal dominant. Breast cancers generally occur in young premenopausal women, whereas ovarian cancers occur at a median age of approximately 50 years.

The breast-ovarian cancer syndrome is caused by germline mutations in BRCA1, which is located on chromosome 17, or BRCA2, which is located on chromosome 13. Lynch II syndrome, a nonpolyposis colorectal cancer syndrome, is associated with mutations in the mismatch repair genes. Adenocarcinomas of the ovary, breast, colon, stomach, pancreas, and endometrium are seen in the families of these individuals.

The use of oral contraceptives has been found to protect against ovarian cancer, possibly because of suppression of ovulation. It has been postulated that incessant ovulation may predispose to malignant transformation in the ovary.

Patients with a known germline mutation (e.g., BRCA1 or BRCA2 mutation) may be offered prophylactic salpingo-oophorectomy once childbearing has been completed, and this operation is highly protective for ovarian and fallopian tube carcinomas. The risk of subsequent breast cancer is also significantly reduced in these women. There is still a small risk of peritoneal carcinoma after prophylactic salpingo-oophorectomy.

The results of some case-control studies suggest that the use of postmenopausal estrogen replacement therapy may increase the risk of ovarian cancer, but these data are controversial.

It has also been postulated that a causative agent could enter the peritoneal cavity through the lower genital tract. For example, the perineal use of asbestos-contaminated talc has been linked to the development of epithelial ovarian cancer. This possibility remains controversial, although tubal ligation and hysterectomy are both associated with a decreased risk of the disease.

Screening for Ovarian Cancer

Population screening for ovarian cancer is not feasible, because ultrasonography and available tumor markers, such as cancer antigen (CA)-125, lack specificity and sensitivity for early-stage disease. CA-125 is more useful in postmenopausal women because false-positive measurements occur commonly in premenopausal women in association with endometriosis, pelvic inflammatory disease, or uterine fibroids. Patients with a strong family history of epithelial ovarian cancer may benefit from surveillance with serial transvaginal ultrasonography and serum CA-125 level measurements.

Symptoms

Unfortunately, many patients in whom ovarian cancer develops have only nonspecific symptoms before dissemination takes place. In early-stage disease, vague abdominal pain or bloating is common, although symptoms of a mass compressing the bladder or rectum, such as urinary frequency or constipation, may bring the patient to a physician. Sometimes the patient complains of dyspareunia. Premenopausal women may experience menstrual irregularity. Only rarely does a patient present with acute symptoms, such as pain secondary to torsion, rupture, or intracystic hemorrhage.

In advanced-stage disease, patients most often present with abdominal pain or swelling. The latter is usually caused by ascites. Careful questioning usually reveals that there has been a history of vague abdominal symptoms, such as bloating, constipation, nausea, dyspepsia, anorexia, lethargy, or early satiety. Premenopausal patients may complain of irregular menses or heavy vaginal bleeding.

Clinically, patients with fallopian tube cancer can present with a vaginal discharge that is typically watery in nature, as well as with vaginal bleeding, pelvic pain, or some combination of symptoms. In postmenopausal patients, the vaginal discharge may be yellow, watery, and similar to that seen with a urinary fistula. A fallopian tube cancer should be suspected in a postmenopausal patient whose bleeding or abnormal cytologic findings are not explained by endometrial or endocervical curettage. In most patients, the diagnosis is not made preoperatively.

Peritoneal carcinomas usually present with abdominal swelling caused by ascites.

Signs

These malignancies are frequently misdiagnosed for several months because of the nonspecific nature of the symptoms. With ovarian cancer, a vaginal or rectal examination will usually reveal a solid, irregular, fixed pelvic mass; if combined with an upper abdominal mass, ascites, or both, the diagnosis is almost certain.