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ORIGINAL RESEARCH |
From the Department of Obstetrics/Gynecology, University of Washington, Seattle, Washington; the Marsha Rivkin Center for Ovarian Cancer Research, Seattle, Washington; and the Fred Hutchinson Cancer Research Center, Seattle, Washington.
Address reprint requests to: Charles Drescher, MD, Fred Hutchinson Cancer Research Center, 1101 Madison Street, Suite 1500, Seattle, WA 98104, E-mail: cdresche{at}fhcrc.org
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Abstract |
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Methods: A population-based sample of 6749 women aged 54–84 years, living in 40 predominately rural communities in Washington state, was surveyed about their utilization of ultrasonography and CA 125 for ovarian cancer screening. We also assessed relevant demographic, family history, psychosocial, and health behavior variables.
Results: After exclusions, data from 4938 respondents were available. Two percent (n = 96) reported having been screened. Multiple logistic regression identified ovarian cancer worry, contact with an obstetrician-gynecologist, and family history of ovarian cancer as independently associated with screening. Based on self-reported family histories, 27 women had pedigrees consistent with high risk of ovarian cancer, but none of those women reported having been screened.
Conclusion: Ovarian cancer screening is rare. Women at high risk of it might not be getting recommended screening.
The value of early detection screening for ovarian cancer using the serum tumor marker CA 125 or transvaginal sonography is uncertain. Transvaginal sonography has reported sensitivity as high as 100% but resulted in 10–20 operations for each malignancy detected.1,2 CA 125 level elevated to at least 35 U/mL is approximately 50% sensitive and 98% specific for early-stage disease.3–5 False-positive screens can cause unnecessary anxiety, surgery, and morbidity. Evidence that screening reduces mortality rate is lacking, although there are at least two current randomized controlled trials.6,7
In 1994, a National Institutes of Health (NIH) consensus conference on ovarian cancer published screening recommendations.8 Routine screening of women without a family history of ovarian cancer was not recommended, although they are candidates for enrollment in screening trials. Screening outside a trial is appropriate for women with at least one first-degree relative with ovarian cancer if they are informed of risks of screening and the lack of prospective data showing benefit. Screening that included at least annual rectovaginal pelvic examinations, CA 125, and transvaginal sonography is recommended for women with family histories consistent with hereditary ovarian cancer syndrome. How closely clinical practitioners adhered to those guidelines is not known.
We surveyed a population-based sample of women from Washington state about ovarian cancer screening. Our objective was to determine contemporary medical practice with respect to ovarian cancer screening and provide information for designing efficient screening programs, should it prove beneficial.
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Methods |
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Follow-up interviews, on which our study was based, were completed successfully in 6749 of 8896 (75.9%) eligible women. Among those excluded, 965 refused to complete the interview, 727 could not be contacted, 455 were too ill, were deceased, or institutionalized. Among the 6749 respondents, we excluded 100 who did not complete questions relating to ovarian cancer screening, 1684 who reported having had a bilateral oophorectomy, and 27 with history of ovarian cancer, leaving 4938 for analysis.
We asked if they ever had a CA 125 blood test to screen for ovarian cancer and if they had an ultrasound examination of the ovaries. Responses included yes, no, don’t know, or refused. Individuals who responded yes were questioned further about the frequency of testing. Respondents were classified as having been screened if they reported at least one CA 125 blood test specifically for ovarian cancer screening or if they had ovarian ultrasounds at least every 2 years. All others were classified as not screened.
We asked about histories of cancer in all first- and second-degree blood relatives and recorded cancer site and age at diagnosis for the first three affected relatives. Family histories were classified as high risk if they were consistent with the American Society of Clinical Oncology Cancer Genetics Task Force guidelines, which included any of the following characteristics: two or more breast cancer cases and one or more ovarian cancer cases diagnosed at any age among first- or second-degree relatives of the same lineage; three or more breast cancer cases diagnosed before age 50 years among first- or second-degree relatives of the same lineage; or sister pairs with two breast cancers diagnosed before age 50 years, a breast cancer diagnosed before age 50 years and an ovarian cancer diagnosed at any age, or two cases of ovarian cancer. Other family history classifications included first-degree family member with ovarian cancer, second- or third-degree family member with ovarian cancer only, or no family history of ovarian cancer.
Demographic, reproductive, family history, psychosocial, and health behavior variables were analyzed for associations with ovarian cancer screening. Demographic variables included age, income, race, and rural versus urban residence. Age was grouped into three levels, 54–64, 65–74, and 75–84 years. Income was recorded as less than $15,000 per year, between $15,000 and $35,000 per year, or greater than $35,000 per year.
Ovarian cancer worry was assessed by asking modified versions of questions developed by Caryn Lerman in prior research on women at risk of breast cancer.10 Participants were asked how often they thought or worried about getting ovarian cancer and how frequently those thoughts affected their moods or daily activities during the preceding month. A four-point monotonic worry scale was created to categorize overall worry as severe, moderate, mild, or none. Worry was classified as severe if women’s thoughts about getting ovarian cancer affected their moods often or all the time, or affected their daily activities sometimes or often or all the time. Moderate worry consisted of thoughts about getting cancer that affected their moods sometimes or if they thought or worried about it often or all the time. Mild worry consisted of thoughts or worries about getting ovarian cancer sometimes. No worry consisted of responses of not at all or rarely to all anxiety questions.
We collected information on medical insurance coverage and health behavior. Respondents were classified as insured if they reported having health insurance or a deductible of any kind. We asked about the types of doctors they had seen in the preceding 2 years, classified as obstetrician-gynecologist (saw an obstetrician-gynecologist at least once), general medicine (saw a general medical doctor at least once and did not see an obstetrician-gynecologist), and none or other (did not see a physician or saw a physician other than a general medical doctor or an obstetrician-gynecologist). Cervical and breast cancer screening services were evaluated by asking whether they had mammograms in the preceding 2 years or Papanicolaou smears in the preceding 3 years.
2 analysis was used to identify factors associated with ovarian cancer screening. Multivariate methods were used to clarify and confirm results of univariate analysis. Logistic regression analyses used variables associated with ovarian cancer screening at the univariate level to estimate the relative odds of having been screened for ovarian cancer. Because of small numbers in certain groups, family history classifications were combined to form a negative family history group (no affected relatives and affected second- or third-degree relatives) and a positive family history group (single affected first-degree relative and high risk) for regression analysis. Mammography and cytology screening services correlated highly with ovarian cancer screening. To avoid confounding because of colinearity of those screening activities with ovarian cancer screening, logistic regression was done including and excluding that variable.
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Results |
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Ninety-three percent of respondents had health insurance and 94% had seen a physician within the past 2 years. Sixty-six percent had a mammogram within the past 2 years, and 67% had a Papanicoloau smear within the past 3 years.
Ninety-six percent (n = 4756) had no relatives with ovarian cancer. A positive family history of ovarian cancer was identified in 182 women, including 139 (3%) with a single affected first-degree relative and 16 with second- or third-degree relatives affected. Twenty-seven women had a family history consistent with high-risk criteria, including 12 who reported two or more cases of ovarian cancer in their families. Three hundred fifteen (6%) were nulliparas. Few women reported being worried about ovarian cancer. Ninety-four percent were classified as having no worry, 4% as mildly worried, and 2% as moderately or severely worried.
Two percent (n = 96) of respondents reported having been screened for ovarian cancer, 48 by CA 125 blood test, 45 by sonography, and three by both tests. Twenty of 51 women who had CA 125 testing reported having been tested at regular intervals, including 12 who were tested at least annually and five who were tested biannually. The rest were tested at less frequent or irregular intervals. All 48 women who had ultrasonography were tested regularly; five were tested twice yearly, 31 annually, and 12 biannually.
Bivariate analysis found significant relationships between ovarian cancer screening and age, income, screening for nonovarian cancers, physician specialty, family history of ovarian cancer, and ovarian cancer worry (Table 1
). Women who reported having been screened for ovarian cancer tended to be younger, have an income exceeding $35,000, were more likely to have received cervical and breast cancer screening, and had seen an obstetrician-gynecologist. Although most (88.5%) screening was in women without a family history of ovarian cancer, those screened were more likely than those not screened to have an affected first-degree relative. None of 27 women with high-risk family histories were screened. Mild levels of ovarian cancer worry were more frequent in individuals who were screened.
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Discussion |
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Those data might overestimate the true prevalence of ovarian cancer screening. Individuals were included as having been screened based on reports of regular ovarian sonography without being asked whether sonography was done specifically for screening. Therefore, we might have included women who were having ultra-sonography for other purposes. With regard to CA 125 screening, individuals were asked about it specifically for ovarian cancer screening, but the accuracy of their reports was not confirmed. CA 125 testing was infrequent or irregular in over half the respondents who reported it.
The design of our initial study excluded women with a history of breast cancer from this follow-up survey. The effect of not surveying those women on our estimate of prevalence of ovarian cancer screening is uncertain. Analysis of limited data from 77 women in whom breast cancer developed between baseline and follow-up surveys indicated that approximately 24% of breast cancer survivors had bilateral oophorectomies and thus were not candidates for screening. Other studies estimated that 5–10% of breast cancers occur among women with hereditary cancer syndromes.11 Most of those women would also be at increased risk of ovarian cancer and be candidates for screening.
The analysis of factors that influenced ovarian cancer screening was limited by the small number of women screened (n = 96). Multivariate analysis found physician specialty, family history, and ovarian cancer worry associated independently with ovarian cancer screening.
Women who were screened were more likely than those who were not to have seen an obstetrician-gynecologist. Unpublished data from a survey of physicians in Washington state indicated that obstetrician-gynecologists were more likely than general medical doctors to recommend screening for women at high risk and to have ultrasound equipment in their offices, which might facilitate screening. General medical doctors also might refer patients to obstetrician-gynecologists for ovarian cancer screening.
Although 88.5% of ovarian cancer screening was among women without a family history of ovarian cancer, those screened were more likely to have a single affected first-degree relative. Screening among them could be considered consistent with NIH consensus guidelines if participants were fully informed of screening risks and that there are no data that show a benefit from screening. None of 27 women with high-risk family histories reported having been screened. Those women had self-reported family histories consistent with at least a 10% probability of a germline BRCA1 mutation in their families.12 The lack of ovarian cancer screening among high-risk women might be explained by failure of physicians to recognize a high-risk pedigree or need for screening, avoidance of screening by the women because of fear of cancer, or less significant family histories collected during personal interviews or medical record review.
Mild worry or thoughts about ovarian cancer were more frequent among those screened (13.5% versus 3.7%), which agrees with finding of Schwartz et al.13 It is not known whether women with mild worry were more motivated to be screened or whether worry was a consequence of screening.
Efficient ovarian cancer screening programs will be essential if screening proves effective. Variations in screening among physician specialties suggests that implementation of guidelines might be inconsistent. Screening is likely to be most beneficial to those at greatest risk. The lack of screening among high-risk women is concerning. Future studies need to identify barriers to screening among women at increased risk.
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Footnotes |
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Received September 30, 1999. Received in revised form January 14, 2000. Accepted February 1, 2000.
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References |
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2. Karlan BY, Raffel LJ, Crvenkovic G, Smart C, Chen MD, Lopez E, et al. A multidisciplinary approach to the early detection of ovarian carcinoma: Rationale, protocol design and early results. Am J Obstet Gynecol 1993;169:494–501.[Medline]
3. Jacobs I, Bast RC Jr. The CA125 tumor associated antigen: A review of the literature. Hum Reprod 1989;4:1–12.
4. Bast RC Jr, Knauf S, Epenetos A, Dhokia B, Daly L, Tanner M, et al. Coordinate elevation of serum tumor markers in ovarian cancer but not in benign disease. Cancer 1991;68:1758–63.[Medline]
5. Einhorn N, Sjovall K, Knapp RC, Hall P, Scully RE, Bast RC Jr, et al. Prospective evaluation of serum CA125 levels for the early detection of ovarian cancer. Obstet Gynecol 1992;80:14–8.
6. Kramer BS, Gohagan J, Prorok PC, Smart C. A National Cancer Institute sponsored screening trial for prostatic, lung, colorectal and ovarian cancers. Cancer 1993;71:589–93.[Medline]
7. Jacobs IJ, Skate SJ, MacDonald N, Menon U, Rosenthal AN, Davies AP, et al. Screening for ovarian cancer: A pilot randomised controlled trial. Lancet 1999;353:1207–10.[Medline]
8. National Institutes of Health Consensus Development Conference Statement. Ovarian cancer: Screening, treatment, and follow-up. Gynecol Oncol 1994;55:S4–14.[Medline]
9. Andersen MR, Yasui Y, Kuniuki A, Meischke H, Etzioni R, Urban N. The Community Trial of Mammography Promotion: An evaluation of the effectiveness of mammography promotion by volunteers in rural communities. Am J Prev Med 2000;18:199–207.[Medline]
10. Lerman C, Trock B, Rimer BK, Jepson C, Brody D, Boyce A. Psychological side effects of breast cancer screening. Health Psychol 1991;10:259–67.[Medline]
11. Szabo CI, King MC. Inherited breast and ovarian cancer. Hum Mol Genet 1995;4:1811–7.[Abstract]
12. Statement of the American Society of Clinical Oncology: Genetic testing for cancer susceptibility. J Clin Oncol; adopted on February 20, 1996;14(5):1730–6; discussion 1737–40, May 1996.
13. Schwartz M, Lerman C, Daly M, Audrain J, Masny A, Griffith K. Utilization of ovarian cancer screening by women at increased risk. Cancer Epidemiol Biomarkers Prev 1995;4:269–73.[Abstract]
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