Screening for Ovarian Cancer

Annekathryn Goodman

The risk of developing epithelial ovarian cancer (the most common form) is far less than that of developing breast cancer and other gynecologic malignancies; the lifetime probability is approximately 1 in 70. However, this cancer has a particularly high case fatality rate. In the United States, of the estimated 22,250 new cases diagnosed annually, there are about 15,500 deaths, giving this cancer the highest death per case ratio of all female cancers. Ovarian cancer deaths among prominent public figures, the availability of promising diagnostic tests, and the general trend toward increased interest in disease prevention among women have focused attention on screening for ovarian cancer. The primary care practitioner needs to understand the epidemiology and risk factors for this disease, as well as the value and limitations of available tests, to respond appropriately to patients’ questions and, when appropriate, recommend a screening intervention.

EPIDEMIOLOGY AND RISK FACTORS (1, 2, 3, 4, 5, 6, 7, 8 and 9)

Increasing age and family history are risk factors for ovarian cancer. The annual incidence is 20 per 100,000 among women aged 30 to 50 years and increases to 40 per 100,000 among women aged 50 to 75 years. The incidence among older women is even higher when one restricts the denominator to women who have not had their ovaries surgically removed.

A family history of ovarian cancer is present in about 10% of women with the disease. Most of these women have a family history of sporadic ovarian cancer. About 5% of ovarian cancers occur among women who are members of families with inherited predisposition to cancer, including those with BRCA1 and BRCA2 mutations. For some subsets of patients with inherited predisposition, cumulative lifetime risk of ovarian cancer may be as high as 85%. For most women with BRCA1 mutation, however, the cumulative risk by age 70 years is closer to 25%. For women with BRCA2 mutation, the cumulative risk is lower—approximately 10% by age 70 years. These risks warrant consideration of prophylactic oophorectomy, as well as regular screening efforts.

A family history of the more common sporadic ovarian cancer also confers risk. The best estimate is that ovarian cancer in one first- or second-degree relative increases risk threefold. When two relatives have had the disease, risk is increased fivefold. Ovarian factor infertility and endometriosis has also been associated with an increased risk of ovarian cancer.

Use of the oral contraceptive pill and parity are associated with reduced risk of ovarian cancer in unselected women. Any use of oral contraceptives appears to reduce risk by 35% and use for five or more years by 50%. A case-control study indicated similar protection afforded to women with known mutations in either the BRCA1 or the BRCA2 gene. Any pregnancy reduces risk by about 50%; increasing number of pregnancies is associated with decreasing risk.

Other factors, including age at first pregnancy, menstrual history, hormone replacement therapy, and dietary factors, may modify the risk of ovarian cancer, but evidence is inconclusive. Tubal ligation and possibly hysterectomy appear to be protective. Inflammatory reactions have been proposed to play a role in malignant transformation of the ovary.

NATURAL HISTORY OF OVARIAN CANCER AND EFFECTIVENESS OF THERAPY (10, 11, 12 and 13)

Natural History

Mortality rates for ovarian cancer have changed little over the last three decades due in part to late-stage clinical presentation. When ovarian cancer is diagnosed after clinical presentation with signs or symptoms, three of four cases have already spread beyond the ovary into the upper abdomen or lymph nodes (stage 3) or to the lungs or liver (stage 4). Of note, 20 % of apparent stage I cancers are upstaged to stage 3 with good surgical staging, underscoring the need for appropriate up-front surgical evaluation.

Once diagnosed with ovarian cancer, many women report having had symptoms referable to the pelvis or to the abdomen prior to the diagnosis. While conventional teaching has suggested that ovarian cancer is a “silent” disease, several case-control retrospective studies have identified a spectrum of symptoms that are present persistently and at great frequency in women diagnosed with ovarian cancer compared to controls. The most common symptoms include abdominal bloating, increased abdominal girth, pelvic and abdominal pain, early satiety, and trouble eating. Women with cancer had these symptoms between 20 and 30 times a month with an odds ratio of 7.4 compared to controls.

Effectiveness of Therapy (see also Chapter 123)

The 5-year survival rate is less than 20% for stage 3 and 4 ovarian cancer. In contrast, the 5-year survival rate of patients with tumor confined to the ovary is greater than 90% in appropriately surgically staged cancers.