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Ovarian Cancer Screening

Friday, October 29, 2010 // Uncategorized

8/9/2009 1:24:49 PM

Bottom Line:  We don’t currently have a good screening test for this type of cancer.

This is the clinical problem as summarized from a recent article in the New England Journal of Medicine:

Ovarian cancer accounts for 3% of cancers in American women, but it is the leading cause of death from gynecologic cancers and the fifth leading cause of all cancer-related deaths among women. The American Cancer Society estimates that 21,650 new cases of ovarian cancer were diagnosed and 15,520 women died of the disease in the United States in 2008.1 In the United States, the lifetime risk of invasive ovarian cancer is approximately 1.4% (1 in 71), and the lifetime risk of dying from invasive ovarian cancer is about 1 in 95.

Two thirds of cases of ovarian cancer are diagnosed in women over the age of 55 years. A family history of ovarian or breast cancer in a first-degree relative approximately triples the risk.2 The risk is particularly high among carriers of a BRCA gene mutation, with a lifetime risk of 39 to 46% among women with the BRCA1 mutation and a risk of 12 to 20% among those with the BRCA2 mutation. The risk is decreased among women who have used oral contraceptives, have been pregnant, or have a history of breast-feeding.

More than two thirds of cases of ovarian cancer are diagnosed when the disease has progressed to stage III or IV and involves the peritoneal cavity or other organs.3 Symptoms that are associated with ovarian cancer are typically nonspecific, and the association is often not recognized until the disease has advanced. In one case–control study, investigators developed an index to try to establish a correlation between symptoms and the diagnosis of ovarian cancer. If women who were 50 years of age or older reported having had pelvic or abdominal pain, urinary frequency or urgency, increased abdominal size or bloating, or difficulty eating or feeling full more than 12 times in a month within the previous year, the index had a sensitivity of 67% and a specificity of 90%. The sensitivity was lower in those with early-stage disease (57%), and the specificity was lower in younger women (87%).4

Current treatment includes surgical resection (debulking), followed by multiagent chemotherapy, usually involving intravenous or intraperitoneal platin compounds and a taxane. Prognostic factors include the stage and histologic grade of the cancer at diagnosis, the presence or absence of residual disease at the completion of the initial surgery, the patient’s functional status and age, and the use or nonuse of platin-based chemotherapy. When ovarian cancer is detected and treated while it is still confined to the ovary (stage I), the 5-year survival rate is approximately 90%, in contrast to the rate of approximately 33% when the disease is diagnosed at stage III or IV. Since ovarian cancer is often initially diagnosed at an advanced stage, when the prognosis is poor even with aggressive therapy, a screening method that facilitates early diagnosis has been actively sought.

What makes a good screening test?  The following are the accepted criteria:

Even is a population at increased risk, there is presently no effective screening test.  The following is a summary from Journal Watch of the most recent study on screening for ovarian cancerin high risk women.

Ovarian Cancer Still Defies Early Detection

CA125 and transvaginal ultrasound were ineffective as surveillance tools for ovarian cancer.

Ovarian cancer mortality rates are high largely because we lack the ability to diagnose this malignancy at an early stage. In a retrospective study, researchers evaluated serum CA125 measurements and transvaginal ultrasound examination as surveillance tools for early detection of ovarian cancer. A group of 341 asymptomatic U.K. women who reported a family history of ovarian cancer were stratified when possible into three risk groups based on genetic records and nature of family history: high (>10% lifetime risk; 179 women); moderate (4%–10% lifetime risk; 77 women); and low (<4% lifetime risk; 71 women). Women were screened annually with serum CA125 measurements and transvaginal ultrasound examinations to detect peritoneal fluid and ovarian masses.

Of 179 high-risk women, 20 carried the BRCA1 mutation, and 11 carried the BRCA2 mutation. Overall, four ovarian cancers (1 detected by screening) and one endometrial cancer occurred during the 9-year study period. Abnormal surveillance results in 30 women led to exploratory surgery; 28 had no malignancy. In high-risk individuals, the positive predictive value (PPV) of transvaginal ultrasound was 1.1%, and the negative predictive value (NPV) was 99.6%; for both tests combined, PPV was 1.3% and NPV was 99.7%. In the entire cohort, the PPV and NPV of transvaginal ultrasound were 0.6% and 99.8%, respectively; for both tests combined, PPV was 1.5% and NPV was 99.8%.

Comment: Although patients who are at high risk for ovarian cancer often demand screening procedures, they should be informed that these procedures are not always useful and often lead to surgery for conditions that turn out to be benign. In any case, transvaginal ultrasound alone seems to be as effectively predictive as both tests combined.

Sandra Ann Carson, MD

Published in Journal Watch Women’s Health January 24, 2008

False positive results on the CA125 and/or vaginal ultrasound may lead to surgical procedures a certain percentage of which  will result in complications.  The search is underway for newer protein markers that can be detected by blood testing.  Several appear promising, but are not ready for primetime.

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