WASHINGTON, DC—Barbara A. Goff, MD—who is credited with showing that ovarian cancer is not silent and does have symptoms—has embarked on a new study with primary care physicians aimed at earlier detection. Speaking here at the Ovarian Cancer National Alliance (OCNA) Annual Conference, Dr. Goff, Director of the Division of Gynecologic Oncology at the University of Washington School of Medicine and a member of the Alliance's Scientific and Medical Advisory Committee, said that systematic medical evaluation of possible ovarian cancer symptoms may be a useful approach until an effective screening test is developed.
The new study is based on the observation that ovarian cancer patients—including 89% of those with early-stage disease—are more likely than control individuals to have medical visits for target symptoms one to six months prior to diagnosis. The symptoms are: abdominal pain; abdominal swelling; gastrointestinal complaints; and pelvic pain.
“As a surgeon, I can tell you that six months makes a real difference,” Dr. Goff said. The aims of the new study are: (1) to determine the acceptability to women of being systematically assessed for potential symptoms of ovarian cancer as part of a primary care visit; and (2) to determine the acceptability of practitioners and office staff of collecting symptom information and referral for early diagnostic testing.
The study will use the Ovarian Cancer Symptom Index, which includes abdominal/pelvic pain, abdominal size/bloating, and difficulty eating/feeling full.
“We're pretty excited about this,” Dr. Goff said. “It's not perfect, but my feeling is that until we have a screening test we need to do something. It's better than doing nothing, and it costs nothing.”
The study will determine the percentage of women age 40-49 and 50 and over who are symptom index positive; the acceptability of index-positive women for referral for transvaginal sonography (TVS) and CA125; and describe the results of CA125 and TVS in symptom index-positive women.
The study will be open to any woman over age 40 who has intact ovaries, who is not pregnant, and who can give informed consent who is attending one of three Seattle health clinics for medical care. Dr. Goff said 3,000 women have been enrolled so far, and the hope is to eventually have 10,000 participants. Cases will be linked to the Surveillance, Epidemiology and End Results (SEER) Registry, which covers 70% of the Washington state population.
“At least in our state, most of the physicians like it,” Dr. Goff said. “There has been no negative impact from practitioners whatsoever.”
She pointed out that if the symptom index is negative, physicians can go on to other potential conditions a woman may have. “People are worried about lots of women going on to surgery. That's not what's going to happen,” she said. “Right now only about 5% of women test positive on the symptom index.”
In her presentation at the OCNA meeting, Dr. Goff noted that when she began linking symptoms with ovarian cancer in studies in the late 1990s, her conclusions were that the majority of women with ovarian cancer do have symptoms; that the majority of women with early-stage disease have symptoms; and that delays in diagnosis are common. In a survey she did in collaboration with OCNA, these conclusions were borne out.
“There was a lot of criticism of our study,” she said. Critics pointed out that there was no control group, that there may have been a recall bias, and that there may have been an advocacy bias on the part of survey participants. Also, since the symptoms of ovarian cancer are relatively vague and could be caused by other conditions, critics said medical clinics would be flooded by women with these symptoms and physicians would be overwhelmed.
But other studies began to come to the same conclusions as Dr. Goff's research did. In 2004, she was coauthor of an article in the Journal of the American Medical Association showing that there is a high frequency of ovarian cancer symptoms in women presenting at primary care clinics. And in 2007 the first national consensus statement on non-specific symptoms suggestive of ovarian cancer was issued by the Gynecologic Cancer Foundation, the Society of Gynecologic Oncologists and the American Cancer Society (OT, 8/10/07 issue).
Dr. Goff cited ovarian cancer risk assessment tools such as the Risk of Ovarian Cancer Algorithm (ROCA) test, presented at this year's ASCO Annual Meeting (OT, 6/10/10 issue), as another promising avenue to improve detection of ovarian cancer at earlier stages. ROCA is a triage algorithm based on age and serial changes in CA125 among healthy women. In the study of 3,238 postmenopausal women presented at the ASCO meeting, the ROCA test had a specificity of 99.9%, but it remains to be validated.
Future Strategies in Population Screening
Another speaker, Robert L. Coleman, MD, Professor and Director of Clinical Research in the Department of Gynecologic Oncology, at the University of Texas MD Anderson Cancer Center, said that future strategies in population screening for ovarian cancer may include serial study algorithms as well as novel biomarkers such as HE4, genome and proteome variables, and novel imaging and prevention.
HE4 (human epididymis protein 4), a biomarker expressed in normal male and female reproductive tract epithelium as well as in pulmonary epithelium, is over-expressed in ovarian cancer. The US Food and Drug Administration has approved an HE4 assay for monitoring the recurrence and progression of ovarian cancer, but not for making a diagnosis of ovarian cancer.
A study by Garnet L. Anderson, PhD, of the Division of Public Health Sciences at Fred Hutchinson Cancer Research Center and colleagues published earlier this year in the Journal of the National Cancer Institute (2010;102;26-38) found that concentrations of the biomarkers CA125, HE4, and mesothelin began to rise slightly three years before a clinical diagnosis of ovarian cancer. But the biomarkers became substantially elevated only in the last year prior to a diagnosis. The stage of the ovarian cancer at the time of diagnosis is not known.
In March of this year a risk-assessment test for ovarian cancer, OVA1, from Quest Diagnostics, Inc., became available. OVA1, which measures the levels of five protein biomarkers in the blood, is the first approved in vitro triage test to help physicians determine the likelihood of a woman's ovarian mass being cancerous or benign. But it is not a screening test.
Like Drs. Goff and Coleman, Michael Seiden, MD, PhD, President and CEO of Fox Chase Cancer Center, who also spoke at the meeting, cited ROCA as a promising addition to ovarian cancer detection. Dr. Seiden said the hope for an effective screening strategy and for more effective treatments for ovarian cancer rests in part with translational research.
He said translational research is important but difficult, since it requires trained scientists and clinical investigators working as teams; patients willing to participate in clinical studies; adequate funding; and often additional regulatory work and regulations.