Combining a symptoms index with CA 125 to improve detection of ovarian cancer

Autor: Kimberly A. Lowe, Nicole Urban, Nathalie Scholler, M. Robyn Andersen, Lindsay Bergan, Barbara A. Goff, Pamela J. Paley, Charles W. Dresher
Rok vydání: 2008
Předmět:
Zdroj: Cancer. 113:484-489
ISSN: 1097-0142
0008-543X
DOI: 10.1002/cncr.23577
Popis: Ovarian cancer is the second most common gynecologic malignancy in the U.S. Greater than 70% of women with ovarian cancer are diagnosed with advanced stage disease, in which the cure rates are only 20% to 30%, making it also the most deadly cancer.1 Fortunately, cure rates for those diagnosed when the disease is confined to the ovary are approximately 70% to 90%.2 Historically, the symptoms of ovarian cancer were thought to develop only after the disease had progressed to an advanced stage. However, recent research has shown that many women with early-stage disease report symptoms and the report of 1 of 3 symptoms that are new to an individual and occur frequently in ovarian cancer may serve to distinguish cancer cases from healthy women.3–5 Although ovarian cancer meets the World Heath Organization’s criteria of a disease that would benefit from screening,6 our current screening modalities have not been shown to reduce the morbidity or mortality of this disease. Currently, the American College of Obstetricians and Gynecologist and the U.S. Preventative Services Task Force recommend against screening for ovarian cancer in average-risk women. The National Institutes of Health (NIH) Consensus Panel on Ovarian Cancer statement also indicated that although currently available screening tests (CA 125 and transvaginal ultrasound [TVS]) should not be used for screening average-risk women outside of research trials, women with a family history of ovarian cancer (ie, those considered to be at an elevated risk) could reasonably choose to pursue screening using CA 125 and TVS. Despite uncertainty regarding the effectiveness of screening using current tests, screening for ovarian cancer was and is encouraged for those women at high risk for ovarian cancer because of a possible BRCA1/2 mutation and who have not chosen to pursue surgical risk reduction.7 Recently, a consensus statement concerning symptoms has come out to encourage the evaluation of ovarian cancer for women with certain symptoms associated with this disease. The effectiveness of several multimodal screening strategies for ovarian cancer using biomarkers (often CA 125) and TVS currently are being studied in several trials.8,9 These strategies generally include the annual (or more frequent) evaluation of blood biomarkers that might indicate the presence of a cancer. In these studies, TVS is generally a second screening tool for women who have positive biomarker results. Screening programs may or may not include the annual routine use of TVS as a first-line screen. Unfortunately, to our knowledge it is unclear how successful these various strategies for screening will be. Although TVS is a very sensitive test, when used as a first-line screen it produces a relatively high rate of false-positive results that require surgical follow-up and a rate of surgeries-per-cancer found that is unacceptable to most clinicians.10 When blood biomarkers are used for first-line screening, women with positive results generally do not go directly to surgery. Instead, TVS is generally used as a second screening step to identify women with false-positive marker results before surgical referral. When TVS is used as a second level of screening, the sensitivity of the multimodal screening program as a whole is limited by the sensitivity of the initial screening biomarker used. CA 125 has been used for this purpose. Unfortunately, CA 125 is elevated above reference levels in only approximately 50% of patients with clinically detectable, early-stage disease.2,11,12 Statistical efforts currently are under way to improve the performance of CA 125,13 as are studies of markers to be used in combination with CA 125 to trigger TVS as a second-stage screening test.14–16 Using a combination of markers to create a composite marker for use as an initial screen could improve the diagnostic performance of a 2-step screening program. In addition, the positive predictive value (PPV) of the screening program could be assured by the use of a second test such as TVS that would identify the majority of the false-positive results among the initial screening results. Efforts to combine CA 125 with other markers have included examinations of CA 125 with HE4, mesothelin, and other markers.14–17 Mesothelin18–21 and HE422,23 may be 2 of the most promising new ovarian cancer biomarkers currently under evaluation. Their diagnostic performance is known and they appear to complement CA 125. Briefly, mesothelin is an epithelial biomarker14 and HE4 is commonly found to be overexpressed in ovarian cancer tissue and elevated in the serum of patients with ovarian cancer.22–24 The current study presents a second report on the results of a study seeking to create a symptom index that could be used to differentiate women with undiagnosed ovarian cancer from healthy women and those with other gynecologic conditions. The prior report described the development of a symptom index in an exploratory dataset and analysis of the sensitivity and specificity of that index in a confirmatory dataset and with a general clinic control group.5 The symptom index thus developed consists of a decision-rule to be used in determining whether symptoms reported by a woman might suggest that she has ovarian cancer. Women reporting symptoms of pelvic or abdominal pain, bloating, increased abdominal size, difficulty eating, or feeling full quickly >12 times per month that have occurred for < 1 year are considered to have a positive symptom index.5 Few women (approximately 2%) in a general clinic sample report symptoms consistent with a positive index score. This report builds on our prior research by determining whether symptom reports might make an independent contribution to the prediction of ovarian cancer in a screening situation when data are also available on CA 125. We hypothesized that the symptom index would identify women with cancer who do not have elevated levels of CA 125 but might benefit from immediate TVS evaluation, and thus might add to the sensitivity of CA 125 and/or other biomarkers as an initial screening marker in a multistep screening strategy.
Databáze: OpenAIRE
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