By Laura Sussman
When diagnosed with ovarian cancer in its most curable stage, Liz Stegall knew someone was watching over her — her dear friend, Linda.
Best friends since meeting as sorority sisters at age 18, together they experienced life events: marriages, raising families, losing loved ones and Linda’s diagnosis with late-stage ovarian cancer.
“Then, no one talked about ovarian cancer. Linda was just 34 when diagnosed and died at 43. I was there when she had her first surgery and her last. We had the same blood type so I even donated blood and platelets. We were just that close,” Stegall says.
Seven years later, when Linda’s family suggested Stegall participate in a study evaluating a simple blood test as a screening tool for the early detection of the disease, her decision to enroll was an easy one.
“They’d heard that MD Anderson was looking for healthy women at low risk and thought I was the healthiest person they knew,” she says. “I had been blessed with good health — no history of gynecologic or other health problems, exercised for 30 years and never smoked — so I participated, in Linda’s memory.”
Old test, new possibility
Via a simple blood test, the study evaluates the protein long recognized for predicting ovarian cancer recurrence, CA-125, and its change over time.
MD Anderson has a long history with this important biomarker. In the 1980s, Robert Bast Jr., M.D., professor, vice president for translational research and the study’s co-investigator, discovered CA-125 and its ability to track ovarian cancer.
“Since then, researchers have been trying to determine its role in early detection,” Bast says. “However, CA-125 can become elevated for reasons other than ovarian cancer, leading to false positives in screening. The marker is shed by 80% of all ovarian cancers.”
Over the last 10 years, there’s been excitement over new markers and technologies in ovarian cancer, explains Karen Lu, M.D., professor in the Department of Gynecologic Oncology and the trial’s principal investigator.
“We thought we’d ultimately find a better biomarker for early detection of the disease. But after looking at new markers and testing them head-to-head in strong, scientific studies, we’ve found none better than CA-125,” she says.
The prospective study enrolled 3,252 women from seven sites, with MD Anderson serving as the lead. All were healthy, post-menopausal women with no strong family history of breast or ovarian cancers. The study’s primary endpoint was specificity, or few false positives.
Participants received a baseline CA-125 blood test. Then, using the Risk of Ovarian Cancer Algorithm, a mathematical model based on their age and CA-125 score, women were stratified into one of three risk groups: low, intermediate and high.
After considering each woman’s CA-125 change over time, researchers determined 85 women to be at high risk. This group received transvaginal sonography and were referred to a gynecologic oncologist. Of those, eight underwent surgery: five had ovarian cancer — three with invasive and two with borderline disease — all in early stage. Of great importance is that the invasive cancers detected were the most aggressive form of the disease and were caught early when the disease is often curable.
Encouraging though not definitive
While encouraging, the findings are neither definitive nor immediately practice changing. A large, randomized prospective trial is ongoing in the United Kingdom. Results from more than 200,000 women should be known by 2015.
In the meantime, MD Anderson’s study continues. Lu and Bast will look at combining other markers with CA-125 to determine the screening impact of their combined change over time.
“As a clinician treating women with this disease for more than 10 years, I’m an admitted skeptic of ovarian cancer screening,” Lu says. “Now, with these findings, I’m cautiously optimistic that, in the not-too-distant future, we may have a screening method that detects the disease in its earliest, curable stages, which can make a difference in the lives of women with this devastating disease.”
Sharing her diagnosis
After six years of annual testing, Stegall’s CA-125 score rose dramatically in July 2009; she was diagnosed with early-stage disease. While thankful that hers was detected when curable, telling Linda’s family, with whom she’s remained close, may have been harder than telling her own children.
“I couldn’t imagine telling them that I also had ovarian cancer,” Stegall says. “They consider me part of the family, and I was worried about putting them through this again. It’s just so surreal. How sad that this research was not done in time to help Linda, but she definitely would have done anything she could for me — and she did.”