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Ovarian cancer is the most frequent
cause of death from gynecologic malignancy in the United States. Approximately
20,700 new cases are diagnosed each year, and 12,500 of these women will die of
their disease. In the United States, one woman in 70 (1.4%) will develop ovarian
cancer during her lifetime compared to one in nine for breast cancer. Symptoms
usually do not become apparent until the tumor compresses or invades adjacent
structures, ascites develops, or metastasis becomes clinically evident. As a
result, 70% of women with ovarian cancer have advanced disease at diagnosis with
a five year survival rate of 15% to 20% compared to the 5 year survival of 90%
in patients with stage I disease. Because of the significant differences in
survival rates between early and advanced cancers, a screening method for
detecting early ovarian cancer has been sought. Clinical evidence suggests that
the preclinical phase for ovarian cancer may be less than two years. This rapid
growth pattern may imply difficulty in detecting early, resectable tumors. Patients at risk include those of low parity, decreased fertility and delayed childbearing. The annual incidence increases with age, from 20 per 100,000 in women age 30 to 50 years of age and 40 per 100,000 in women 50 to 75 years of age. The strongest risk factor for ovarian cancer is familial evidence of ovarian cancer, reported in 7% of women with the disease. A patient with a history of familial ovarian cancer (two or more first-degree relatives-mother, sister, daughter) may have as much as a 50% chance of developing the disease. The presence of a hereditary ovarian cancer syndrome includes occurrence of ovarian, breast, and/or related cancers such as endometrial and gastrointestinal (Lynch II syndrome) in multiple members of two to four generations. These women present with the disease at an earlier age (45 to 52 compared to 59 years in the general population). The risk of ovarian cancer is elevated among women who have a first-degree relative with breast cancer (1.5 times) or colorectal cancer (1.9 times). Women with a positive family history and a familial tendency for ovarian cancer should be counseled in their early 20s by a gynecologic oncologist or geneticist about their risk, with clinical follow-up in their 30s and possibly preventive surgery (i.e., prophylactic oophorectomy). Patients in the reproductive age group may be counseled on the benefits of oral contraceptives. Studies have demonstrated a decrease in ovarian cancer risks (as high as 50%) in patients taking oral contraceptives, with the protective effect increasing with duration of use. Current screening tests for detecting ovarian cancer include physical examination, tumor markers (e.g., CA 125) and imaging methods such as US: transabdominal (TAS) and transvaginal (TVS) with color Doppler and power Doppler imaging, CT, and MRI. The pelvic examination, which can detect a variety of gynecological disorders, is not sensitive or specific for detecting ovarian cancer. In general, ovarian malignancies have disseminated by the time they are palpable. CA 125 is the antigenic determinant of a glycoprotein expressed by epithelial ovarian tumors and other tissues of müllerian origin. CA 125 is elevated (> 35 U/mL) in more than 80% of patients with epithelial ovarian cancer, however; it is only 25% sensitive for early disease. It is not specific for ovarian cancers since it can be elevated in other malignant conditions (pancreatic, endocervical, and fallopian tube cancers) and in benign conditions such as pregnancy, endometriosis, leiomyomas, pelvic inflammatory disease, hepatitis, and cirrhosis. CA 125 fluctuates during the menstrual cycle, and in premenopausal women, more than 90% of CA 125 elevations are falsely positive for ovarian carcinoma. Therefore, alone it does not have a sufficiently high sensitivity to be recommended for routine ovarian cancer screening. However, CA 125 levels exceeding 65 U/mL are predictive of malignancy in 75% of postmenopausal women with pelvic masses. The primary usefulness of CA 125 is in the management of patients with documented ovarian cancer. Other tumor markers such as NB/70K, a marker for epithelial mucinous adenocarcinomas of the ovary, may increase the sensitivity of the CA 125 marker when used concurrently. Data have confirmed that US is a more accurate method of distinguishing normal from abnormal ovaries, especially in the postmenopausal female. The largest study to examine TAS for ovarian cancer was reported in 1989. In this study, premenopausal and postmenopausal women had three annual transabdominal ultrasound examinations; 338 had abnormal screening; five primary ovarian cancers and four metastatic ovarian cancers were detected for an overall specificity of 97.7%. Two of the primary cancers were found at the first screening and three a year after the first screening. One in 50 women with abnormal US had ovarian cancer, which means that of 50 laparotomies one case of primary ovarian cancer would be found with no cancer present in the other 49. The study demonstrated the usefulness of TAS for detecting ovarian abnormalities particularly in postmenopausal women, and its lack of specificity due to its suboptimal resolution of the morphological features. Researchers in another study screened 22,000 asymptomatic postmenopausal women with a combination of both CA 125 and TAS. Their screening program had a specificity of 99.9% with sensitivity of 78.6% at one year and 57.9% at two year follow-up. By placing a high frequency transducer closer to the adnexa, TVS increases resolution and improves the ability to detect abnormalities of the ovary. In a study of postmenopausal females, researchers found that TVS was able to identify both ovaries in 60% of the cases and at least one ovary in 81% of the cases. Most of the ovaries not visualized were atrophic. These data suggest that not visualizing the postmenopausal ovary with TVS confirms lack of an abnormality. TVS has demonstrated that 17% of postmenopausal ovaries contain simple cysts that are transient and frequently benign. The prevalence of these adnexal cysts or cyst activity is independent of hormone replacement therapy. While scanning 1,300 asymptomatic patients with TVS, researchers in another study identified two early ovarian cancers with normal CA 125 and pelvic examination. In an attempt to improve the specificity, one study evaluated women with positive family history (one first-degree or second-degree relative) of ovarian cancer with TVS. Three primary stage I ovarian cancers were found, consistent with a false positive rate of 5.5% and a positive predictive value (PPV) of 7.7%. Another study found that 32 surgeries were performed to diagnose ovarian cancer in the low risk population compared to 17 surgeries in the high-risk population. Combining TVS with color flow Doppler imaging technique has been shown by many authors to further enhance the detection of early stage ovarian cancer. In a high-risk population, one study found TVS to have a specificity in detecting ovarian tumors of 97.5% and PPV of 25% compared to color flow imaging with a specificity of 99.9% and PPV of 60%. The pulsatility or resistive index (PI or RI) value indicates decrease in resistance to blood flow in the distal vasculature and has been identified in malignant lesions as well as vascular benign masses. The neovascularity identified in malignant masses can also be seen in the formation of the corpus luteum. Therefore, to avoid unnecessary surgery, screening for premenopausal women should be done during days 1 to 12 of the menstrual cycle. In postmenopausal women, low resistance blood vessels are not seen within normal ovaries and when present are considered abnormal. The absence of intraluminal flow or high impedance flow in an ovary can potentially exclude malignancy. However, morphologic characteristics remain the most important criteria in differentiating a normal from an abnormal ovary. Pelvic CT is not indicated for screening due to its inability to image small lesions, poor soft tissue discrimination in the pelvis, high cost and need for contrast material. The cost of MRI, in addition to the lack of resolution in the pelvis precludes its use in screening for small ovarian abnormalities. In 1996, the cost of an US screening program prompted by an abnormal CA 125 level was estimated to be six times greater in the general population compared to patients with family history. The cost of screening for ovarian cancer is at least 10 times that of screening for breast cancer. Of every 10,000 women participating in an annual screening program with CA 125 for 3 years, 800 would have an ultrasound scan because of an elevated CA 125, 30 would undergo surgery because of an abnormal ultrasound, and 6 would have ovarian cancer detected at surgery (3 will be diagnosed at early-stage disease and have a chance of a cure. In postmenopausal women, surgical evaluation may be recommended when the ovarian volume is enlarged (> 8 cc) with an elevated CA 125 or a normal CA 125 with abnormal morphologic characteristics of the ovary (i.e., complex or solid mass). If an ovarian simple cyst measures > 5 cm in diameter or < 5 cm with an elevated CA 125 and/or low impedance flow, surgical intervention may be considered. Since there is a low prevalence of the disease in the general population, there are no statistically significant data to show that screening reduces mortality. Additionally, a screening test with high sensitivity is needed. Therefore, routine screening for ovarian cancer cannot be recommended. The results from a large clinical trial comparing long-term mortality from ovarian cancer between screened and nonscreened cohorts are needed. Future developments in serum proteomes may offer exciting opportunities for identifying novel biomarkers or patterns of markers that will have a greater sensitivity and lead time for preclinical disease. Abbreviations CT, computed tomography MRI, magnetic resonance imaging US, ultrasound CLINICAL ALGORITHM(S) Algorithms were not developed from criteria guidelines. | ||
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