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The Disease that Whispers

It’s called “the disease that whispers.” Its incidence is relatively low, its symptoms are easily misattributed, and when it’s discovered, it’s often too late. By many accounts, ovarian cancer, a disease responsible for more deaths than any other type of female reproductive cancer, is a quiet killer.

“The symptoms are vague, they whisper, they don’t speak loudly, but they’re there,” said Fidel Valea, M.D., associate professor and fellowship program director of the Division of Gynecologic Oncology and residency program director of the Department of Obstetrics and Gynecology at Duke University Hospital, during the 9th Annual Susan Patricia Teck Memorial Lecture, April 11.

The unremarkable symptoms that characterize ovarian cancer — bloating, constipation, abdominal pain, gas, indigestion, loss of appetite, and irregular periods, to name a few — are just some of the reasons why the disease is so difficult to detect, said Valea.

The condition is also challenging to study with great reliability because its incidence is relatively low. And, though the disease does have a hereditary component in some cases, predisposition to it can’t be identified by any one biomarker.

“Sixty-five percent of patients with ovarian cancer come in with advanced stages of the disease,” said Valea.

But the fight against ovarian cancer is far from a lost cause. Improved awareness of its symptoms among health care professionals and advancements in screening techniques can contribute to better outcomes, he said.

The symptoms of ovarian cancer might mirror other conditions like premenstrual syndrome,  but women with ovarian cancer tend to experience more of them and with greater severity, said Valea. “Abdominal distention is what tips the scale,” he added. “The problem is, if you wait for symptoms, it’s probably too late.”

But catching ovarian cancer early isn’t easy. Much more so than more common cancers, screening the general population for ovarian cancer results in a high rate of false positives and can lead to unnecessary surgeries that cause more problems than they fix, said Valea. One study, for example, estimated that a hypothetical test with 100 percent sensitivity and 99 percent specificity would result in a positive predictive value of only 3.8 percent. That means that, out of every 100 patient with an abnormal result, less than four would actually have ovarian cancer.

Another drawback to ovarian cancer screening is the absence of a genetic biomarker. While considerations like family history do influence a woman’s risk for the disease, many women acquire it from an ambiguous mix of factors. “There are genetically inherent things or genetic mutations in your own genome that predispose you to cancer,” said Valea. “The little hits add up.”

Valea supported using a combination of screening methods among high-risk populations. “The best bet here is to try to identify the high-risk patients,” he said. “Those are the people that we’re going to have the most impact on.”

The ROCA method, which involves a CA-125 blood test and then referral to additional tests and specialists as needed, for example, seems to be a promising way to identify and monitor high-risk patients. Valea was also optimistic about the potential of a screening test for HE4, a newly identified gene, to help triage patients into high-risk groups.

When it comes to treating ovarian cancer, gynecologic oncologists face the same challenges as other types of oncologists, said Valea. The same molecular pathways that support cancer growth are needed to keep the body alive. Targeting these pathways with therapeutics needs to be done with caution.  “We are always asking how much do we need versus how much does the cancer need,” he said.

Overall, Valea encouraged clinicians to keep a sharp eye out for the symptoms of ovarian cancer and to use screening tests as triage tools rather than as identifiers of disease. “When you tell a woman that she has an abnormal result, you change her life forever,” whether or not the mass is malignant, he said. “You have to be cognizant of how these tests affect the patient.”