Ovarian cancer: Scientists join hunt to identify 'silent killer'

August 31, 2013 | by Roberta Nichols

Ovarian cancer, known as "the silent killer," can perform its lethal work undetected thanks to its neighborhood.

Cancer in the ovaries, highlighted here, can grow undetected in large part because there's so much room in which it can develop. Cancer in the ovaries, highlighted here, can grow undetected in large part because there's so much room in which it can develop.

"The abdomen and pelvis have so much potential space where tumors from the ovary can potentially grow,"  said Ernest Han, M.D., Ph.D., assistant professor and surgeon in the Division of Gynecologic Oncology at City of Hope.

This year in the U.S. alone, ovarian cancer will kill 14,030 women, be diagnosed in 22,240 women, and will begin growing in many others.

Women may fail to recognize or simply dismiss symptoms caused by the intruder: bloating, swelling, pelvic or abdominal pain; feeling full quickly, constipation and urinary frequency. Yet, sometimes the symptoms are too general and gradual to cause alarm. "Every woman at some point in her life has experienced these symptoms," said Han.

"These symptoms are primarily concerning if they are of recent onset [within a few months rather than having occurred for a long time], and if they occur more than 12 times per month," said Robert Morgan, M.D., co-director, Gynecological Oncology/Peritoneal Malignancy Program at City of Hope.

We asked City of Hope experts about the future of ovarian cancer screening and treatment, as well as what women should know about the disease:

How has diagnosis of ovarian cancer changed in recent years?

"Unfortunately, we haven’t made much impact on diagnosis," said Han. "We’re finding this too late – with women in advanced stages. We still lack screening tools for ovarian cancer."

For years, a biomarker called CA-125 has been used to help detect ovarian cancers, yet its presence is frustratingly nonspecific. "There’s a whole laundry list of benign conditions [such as endometriosis or fibroids] that can cause elevations of your CA-125," Han said.

Some good news has emerged of late, however.

In a study recently published in the journal Cancer, researchers explored using CA-125 with ultrasound to screen for ovarian cancer. The pairing had been tried before with disappointing results, but in this study of 4,000 patients tracked over 11 years, researchers obtained much more promising results. Through this two-stage screening method, they accurately ruled out false-positive tests of ovarian cancer in postmenopausal women. A larger study involving 200,000 women is underway in the United Kingdom, and the results should be available in 2015.

Meanwhile, in the quest for accurate screening tools, City of Hope is currently enrolling patients in the Novel Markers Trial, a multicenter observational study testing CA-125 as well as a new marker called  Human epididymis protein 4 (HE4), an epithelial ovarian cancer serum marker. The trial is designed to help scientists develop a better biomarker blood test for ovarian cancer screening.

What are the advances in treatment?

To combat this late-stage adversary, surgeons and oncologists are using more aggressive tactics, such as delivering intraperitoneal chemotherapy following surgery.

"One major treatment advance has been the development and documentation that intraperitoneal chemotherapy improves survival," said Morgan.

"Three previous clinical trials have supported evidence that we should be giving intraperitoneal chemotherapy for all ovarian cancer patients," said Han. However, due to logistical difficulties in administering intraperitoneal chemotherapy, along with the significant side effects, many physicians do not prefer this treatment option.

"The gynecologic oncology group just completed a large phase III trial in the U.S. that featured a modified intraperitoneal dosing that’s potentially more tolerable and easier to administer on an outpatient basis," said Han. "The results of the trial are expected to be released in the near future and should provide important evidence on how should be managing our ovarian cancer patients."

Thanh Dellinger, M.D., assistant professor in the Division of Gynecologic Oncology at City of Hope, is initiating a protocol for a new clinical trial evaluating the effectiveness of heated intraperitoneal chemotherapy in ovarian cancer patients.

The study, led by Dellinger, will explore whether patients’ survival improves if physicians circulate hot chemotherapy directly into the peritoneal cavity following surgery, and its impact on patient quality of life. Currently used for some gastrointestinal cancers, the procedure is believed to result in improved survival given its direct infusion into the peritoneal cavity and improved effect at elevated temperatures.

What are the risk factors for ovarian cancer?

The primary risk factor for ovarian (and endometrial) cancer is familial inheritance, but these occur in only about 15 percent of these cancers.

"The familial syndromes include BRCA [breast cancer antigen mutations 1 or 2] and HNPCC [Hereditary nonpolyposis colon cancer], which also predisposes to ovarian or endometrial cancers," Morgan said. "Other risk factors include infertility and never being pregnant."  

Some women with mutations on the BRCA1 or BRCA2 genes, such as actress Angelina Jolie, opt to remove their breasts and ovaries before actually receiving a cancer diagnosis. Removing the ovaries and fallopian tubes (salpingoophorectomy) has been shown to dramatically decrease the chances of developing breast and ovarian cancers in patients with BRCA mutations.

What is the main thing that people DON’T know about ovarian cancer?

"Ovarian cancer is more difficult to treat because most cancer is diagnosed in later stages, but even in patients who recur, there is hope because therapies given for recurrence can improve length and quality of life," Morgan said.

Further, women have multiple treatment options, such as intraperitoneal chemotherapy, though not all medical centers offer such therapies.

"Patients who wish to be the most aggressive should consult an institution that is familiar with this approach," Morgan said.

What kind of progress should people expect in the next five to 10 years?

"The major change that I expect to see is the further understanding of the biology of ovarian cancer and the development of targeted new treatments," Morgan said.

The increasing use of immunotherapy also may lead to better long-term outcomes.

"Novel methods [perhaps the use of canines or mechanical sensors of tumor specific odors] may help the early detection processes, which have been unsuccessful up to now," Morgan said.

Through the increasing use of minimally invasive robotic surgery, gynecologic cancer patients will hopefully have faster recovery with less disruption to their lives, Han added.

"For patients who have recurrences or metastases, I hope we have more effective drugs with fewer side effects," he said.

Han is working with John Yim, M.D., an associate professor and surgeon in the Division of Surgical Oncology, in developing a natural product that’s showing promise in the laboratory against breast, ovarian and uterine cancer cells. He and his colleagues hope to one day offer it to patients.

What is your take-home message about ovarian cancer?

"Don’t ignore your symptoms," Han said. As with any cancer, he said, "if you can find it early, you have a better chance of fighting it and beating it."

It’s not only imperative to find it early, but to seek out experts to treat it.

"The up-front surgery for gynecologic cancers should be performed by a board certified gynecologic oncologist," Morgan said. "Data demonstrates that there is a marked improvement in long-term outcomes when gynecologic oncologists perform the surgery."

"More research support is necessary to improve the long-term outcomes in ovarian and other gynecologic cancers," he said, adding that clinical research for ovarian cancer needs to be done earlier in the trajectory of drug development.

Said Han: "Ovarian cancer is a bad disease. We’re doing better; we’re keeping them alive. We treat patients constantly through surgery and chemotherapy, but it’s an ongoing, continuous battle."

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