Ovarian Cancer Screening Focuses on Improving Early Detection

The Ovarian Cancer National Alliance states that approximately 20,000 American women receive an ovarian cancer diagnosis annually, with about 15,000 dying of the disease. This high fatality rate is attributable to vague or absent premalignant signs and symptoms early in the disease and screening methods that often fail to detect early stage cancer.

Jacques Abramowicz, MD, director of obstetrical and gynecological ultrasound at Rush University Medical Center in Chicago, explains that if physicians are able to catch ovarian cancer during stage I, the 5-year survival rate is greater than 90%. Unfortunately, between 60% and 70% of ovarian cancers are not diagnosed until stage III or IV, where the survival rate drops to as low as 10%.

“When you do a pap smear and find some changes in the cells, that’s a potential sign for future cancer, and we can do something about it,” Abramowicz says. “We don’t have something like that in the ovaries. And you can tell a woman to examine her breasts every month, but you can’t do that for the ovaries.”

Screening test shortcomings

Testing for CA-125 levels in the bloodstream has been considered the gold standard for ovarian cancer screening in recent years. While this test may be able to detect epithelial ovarian cancer, the most common form of the disease, the test is nonspecific. According to Abramowicz, CA-125 can be found in many tissues, including the uterus and around the lungs. In addition, many conditions are known to increase CA-125 levels, such as endometriosis, and even normal menstruation; thus, it is not the most useful biomarker.

Combining ultrasonography with the CA-125 blood test offers some improved screening results, but not for early stage disease. For example, the results of a study published in the April issue of Obstetrics and Gynecology found that while 60 of 89 cancers were diagnosed using this screening modality, 72% of these cancers were detected at an advanced stage. The study also found that screening often leads to unnecessary biopsies and other surgical procedures. “There’s a certain number of surgeries which are considered acceptable in order to find one cancer,” Abramowicz says. “If we do 10 surgeries and find one cancer, we’re sort of willing to accept that number.” The aforementioned study found a surgery-to-cancer ratio of 19.5:1. According to Abramowicz, “That’s very high. You want a screening test to be good enough so you don’t need to do too many unnecessary surgeries.”

Screening can save lives

Despite the limitations of screening for ovarian cancer using a combination of CA-125 levels and ultrasonography, this screening method can save lives. Jennifer Fox, director of marketing and communications for OrthoIndy and the Indiana Orthopaedic Hospital in Indianapolis, is an ovarian cancer survivor who recently celebrated her 5-year anniversary of being cancer-free, and she credits ultrasonography for helping to catch her stage I cancer.

“For about 10 years, I had a lot of bladder issues—urinary tract infections, kidney infections—and it got to the point where I was having them twice a month,” Fox says. “I was on a lot of antibiotics, and I became allergic to many of them.” Eventually, an ultrasound revealed that a 7-lb tumor had engulfed one ovary. The tumor was located above Fox’s bladder, promoting bacteria build-up, which resulted in the repeated infections. A subsequent blood test revealed high CA-125 levels, indicating the likelihood that the tumor was cancerous, and surgery was performed.

“From oncologists I’ve spoken with, it was pretty outstanding that they found [the cancer] when they did,” Fox says. “I know insurance companies don’t want to be giving ultrasounds to everyone. But if women are presenting with certain issues, I think it’s such a small price to pay. The fact that I had one probably saved my life.”

New data

Several efforts are currently underway to improve early screening for ovarian cancer. Results of a trial published in Gynecologic Oncology found that the combination of Fujirebio Diagnostics blood tests for HE4 and CA-125 were able to identify patients who were at high or low risk for developing ovarian cancer (http://tinyurl.com/nytwpn). The HE4 assay was recently cleared by the FDA as an aid for monitoring recurrence of epithelial ovarian cancer, and it is thought that combining the HE4 and CA-125 tests may enable physicians to preoperatively identify those patients with a high risk of malignancy. This protocol is currently being reviewed by the FDA.

On another front, New York-based MabCure Inc., a biotechnology company, is making progress in developing monoclonal antibodies (MAbs) for the detection of cancer at an early stage. MAbs bind to antigens on the surfaces of cancer cells. “Cancer cells partly shed these antigens into the blood stream,” explains Amnon Gonenne, MD, CEO of MabCure. “We’re looking for these circulating antigens. We want to come up with a test so when a woman goes for a pap smear once a year, she can have a vile of blood taken and analyzed for the presence or absence of these antigens, which are recognized by our antibody.” The company is planning to begin its first full-scale clinical study of 150 patients at high risk for ovarian cancer. According to Gonenne, the objective of the study is to demonstrate “the potency of our MAbs in detecting [ovarian cancer] in a larger patient population and selecting those MAbs with the highest specificity and sensitivity. These MAbs will become the ultimate candidates for the early diagnosis of [ovarian cancer]. The initial draft protocol and budget have been approved, and we are presently working on the final protocol and associated documents required by the hospital Institutional Review Board.”

Take-home message

While ovarian cancer screenings using CA-125 measures and ultrasonography are limited and generally fail to fi nd cancer at an early stage, this protocol can save lives. In the near future, more sensitive and specific diagnostics may become available, as several companies are working on identifying biomarkers that will better determine ovarian cancer risk.