August 26, 2013 | by Nicole White
Early detection of ovarian cancer has the potential to save many women’s lives because, like most cancers, the disease is easier to treat when it’s caught early. But early symptoms of ovarian cancer mirror those of less serious conditions, and an accurate testing strategy has been elusive.
A new study, published online Aug. 26 in Cancer, a journal of the American Cancer Society, shows promise for a detection strategy combining a blood test with an ultrasound exam. One City of Hope expert called the results encouraging, saying it has the potential to detect early-stage ovarian cancer without high numbers of false-positives.
Because ovarian cancer is relatively rare – about one in 2,500 post-menopausal women in the United States will be diagnosed in her lifetime – any screening that causes a large number of false-positive results would harm more women than it helps.
Currently, physicians have no easy way to biopsy ovaries, and accurate diagnosis requires the ovaries to be removed. For this reason especially, experts are cautiously optimistic about the new study results, and are now awaiting results from a similar but much larger study being done in the United Kingdom. That study is expected to conclude in 2015.
“The approach is certainly promising,” said Robert Morgan, M.D., co-director of the Gynecological Oncology/Peritoneal Malignancy Program at City of Hope. But as with most doctors, he wants more results, saying “This method isn’t ready yet for clinical adoption.”
The new study, led by M.D. Anderson Cancer Center in Houston, used a computer program to calculate the risks and benefits of screening women for ovarian cancer. Researchers divided women into three risk groups – low, intermediate and high – based on a blood test measuring CA-125, a protein shed by tumor cells.
More than 4,000 postmenopausal women took the test and researchers followed them for 11 years. Each year, those who fell into the low risk category – most women – would repeat the blood test the following year. Nearly 6 percent tested were deemed “intermediate” risk, and repeated the blood test three months later. An average of 0.9 percent were “high risk.” Those women underwent an ultrasound exam of the ovaries.
Ultimately, 10 women had surgery based on the results. Four were diagnosed with early-stage ovarian cancer, one had Stage I endometrial cancer and the remaining five had other ovarian tumors.
More research is the next step, including the United Kingdom study involving 200,000 women.
“The European study, which is based on these same hypotheses, tests many more women, and we will have to wait for this data,” Morgan said.
The study shows that researchers were able to identify patients with ovarian tumors at earlier stages than would be expected by clinical criteria alone, he said. The major problem with previous studies has been that 30 to 50 surgeries would have to be completed to find even one potentially curable ovarian cancer.
“Most feel that about 10 surgeries to one diagnosis would be acceptable,” Morgan said. “The results of this study suggest that even fewer surgeries may be possible.”
Other treatment avenues
Identifying multiple biomarkers – in addition to the protein relied on in this study – would also be useful in identifying ovarian cancer at earlier stages. Morgan adds that some unconventional strategies might be important to ovarian cancer diagnosis.
“At least 80 percent of patients with this malignancy are diagnosed at a late stage, and despite advances in treatment, aggressive surgery and toxic chemotherapy are necessary to cure even a small percentage,” Morgan recently wrote in an opinion piece in the Journal of the National Comprehensive Cancer Network. In that article, he voiced support of research finding that dogs may be able to sniff out some cancers.
In the study about which Morgan wrote, a Riesenschnauzer dog was trained to detect the difference between ovarian cancer and nonmalignant tissue in petri dishes with nearly 100 percent sensitivity and specificity. The same lab later showed that the odor was present in the peripheral blood of patients with ovarian cancer, suggesting that the animals might be able to detect the presence of ovarian cancer in women themselves.
Several other studies have examined the phenomenon, and the low-tech, low-cost, nontoxic approach has promise, Morgan says.
Or, as a colleague of his quipped: “Now instead of a CAT scan, I will have a dog scan?” Said Morgan in response: Actually, a modern “PET scan.”
While study continues on the diagnostic front, researchers are also seeking new ways to treat ovarian cancer, which is the fourth most common cancer in women, with about 22,000 new cases and 15,000 deaths per year in the U.S. The five-year survival rate for advanced ovarian cancer is 30 percent.
City of Hope is one of two centers in a clinical trial investigating the safety and effectiveness of treating patients with their own T cells that have been engineered to ramp-up their anti-tumor properties.
The cells are modified so that they express a receptor for a protein that is a known cancer antigen. The technology was developed by Adaptimmune, which is also funding the study. The same treatment is also being studied for sarcoma and myeloma.
The ovarian cancer trial, which began this summer, will include patients who are resistant to chemotherapy or have received more than two lines of chemotherapy for their cancer. The patients are infused with the engineered T cells after a high dose of “lymphodepleting” chemotherapy to prepare the immune system for the gene-modified T cells.
Detecting ovarian cancer is a large part of the battle against the disease, but not all of it.
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