Ueland.qxp 22/12/08 11:06 Page 62
Gynecologic Oncology
A Biomarker Panel for Risk Stratification of Ovarian Tumors
a report by
Fred Ueland, MD
Associate Professor, and Director, Gynecologic Surgery, Markey Cancer Center, Whitney-Hendrickson Women’s Cancer Facility, University of Kentucky
Ovarian tumors are being detected with increasing frequency in women of all decision of whether to refer is particularly challenging in pre-menopausal
ages. There are numerous publications emphasizing the importance of a women, who generate the majority of cystic ovarian tumors yet account for
gynecologic oncologist in the care of women with ovarian cancer. The National only 25% of ovarian cancers.
Comprehensive Cancer Network (NCCN),
1
the Society of Gynecologic
Oncologists (SGO),
2
and a number of other organizations recommend that Currently, the decision for operative removal of an ovarian tumor, and whether
women with ovarian cancer be under the care of a gynecologic oncologist. a generalist or specialist should perform the surgery, is based on interpretations
Unfortunately, for a large percentage of women with ovarian cancer, their of physical examination, pelvic imaging studies, laboratory tests, and clinical
initial surgery is not performed by a gynecologic oncologist. A recent study opinion. Pelvic examination alone is inadequate to reliably detect or
supports the effectiveness of a new biomarker panel that helps physicians differentiate ovarian tumors, particularly in the early stages when ovarian
decide which women who require surgery for an ovarian tumor should be cancer is most likely to be cured.
17
Pelvic ultrasound is frequently used, but has
referred to a gynecologic oncologist. limitations in consistently identifying malignant tumors. In general, unilocular
cysts are likely to be benign, whereas mostly solid tumors and cystic ovarian
Recent publications on breast, bladder, gastrointestinal, and ovarian cancers tumors with internal papillary projections are more likely to be malignant.
18,19
have reported improved outcome when cancer management involves a The American College of Obstetrics and Gynecology (ACOG) and the SGO
surgical specialist.
3–8
In addition, a recent meta-analysis of 18 ovarian cancer have published guidelines for patient referral. These guidelines include: patient
studies found that the early involvement of a gynecologic oncologist, rather age, CA125 level, physical findings, imaging study results, and family history.
than a general surgeon or general gynecologist, had a beneficial effect on These recommendations have been evaluated both retrospectively
20
and
patient outcomes. The authors concluded that: subjects with early-stage prospectively.
21
Dearking et al. concluded that the guidelines were useful in
disease are more likely to have comprehensive surgical staging, allowing for predicting advanced stage ovarian cancer but performed poorly for early-stage
better selection of subjects requiring adjuvant chemotherapy; subjects with disease and in pre-menopausal women. It is not known how readily these
advanced disease are more likely to receive optimal cytoreductive surgery; and recommendations are utilized by practicing physicians.
subjects with advanced disease have an improved median and overall five-year
survival.
9
The NCCN practice guidelines,
10
SOGC clinical practice guidelines,
11
CA125 is the most commonly used blood marker for the detection of ovarian
National Institutes of Health (NIH) Consensus Development Panel on Ovarian cancer. While cleared by the US Food and Drug Administration (FDA) for use in
Cancer,
12
the Standing Subcommittee on Cancer of the Medical Advisory monitoring patients after their diagnosis of ovarian cancer, it has yet to be
Committee, and several other published statements
13–15
all recommend that approved as a screening or diagnostic test for ovarian cancer. Two limitations
women with ovarian cancer be under the care of a gynecologic oncologist. of CA125 are its modest sensitivity (~50%) for early-stage ovarian cancer and
Today, only a fraction of women (an estimated 33%) with malignant ovarian in the 20% of ovarian malignancies that fail to express CA125, and its low
tumors are referred to gynecologic oncologists for their primary surgery.
16
specificity. Nonetheless, it is often utlized in clinical practice for pre-operative
decision-making. When markedly elevated (>200U/ml), CA-125 II may be a
Physicians are commonly faced with the question of whether an ovarian tumor useful predictor of cancer, but more often indeterminate CA125 II values
is at high risk for malignancy and warrants referral to a cancer specialist. (35–200U/ml), especially in pre-menopausal women, are misleading. Uterine
Numerous guidelines and management algorithms have been published to fibroids, endometriosis, or any inflammatory process may result in low to
determine the risk for malignancy,
13,22–27
but only 30–40% of ovarian cancer moderate elevations of CA-125 II.
patients are estimated to be treated initially by a gynecologic oncologist. The
Sonographic imaging is an important part of the work-up of women with
ovarian tumors. A variety of ‘morphology indices’ have utilized various
Fred Ueland, MD, is an Associate Professor and Director of
Gynecologic Surgery at Markey Cancer Center, Whitney-
components of imaging, including tumor density, tumor size, and cyst wall
Hendrickson Women’s Cancer Facility, University of Kentucky. His characteristics. While promising, ovarian sonography is not yet universally
main interests are ovarian cancer, proteomics, and transvaginal
integrated into clinical practice. The risk of malignancy index (RMI) combines
ultrasound. Dr Ueland received his MD from Wake Forest
University School of Medicine, and is board-certified in obstetrics
imaging, CA125, and menopausal status to derive a single value score that
and gynecology and gynecologic oncology. describes the likelihood of malignancy. It is used more commonly in Europe
E:
fredueland@yahoo.com
than in the US. More recently, multiparameter indices have been described that
take into account imaging, blood tests, and clinical characteristics.
28
62 © TOUCH BRIEFINGS 2008
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