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U.S. Preventive Services Task Force Reaffirmation Recommendation Statement
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific clinical preventive services for patients without related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
This article was first published in Annals of Internal Medicine (Ann Intern Med 2012; 11 Sept). Select for copyright and source information.
|Task Force Ratings
Strength of Recommendations and Quality of Evidence
Summary of Recommendation and Evidence
The USPSTF recommends against screening for ovarian cancer in women (D recommendation).
This recommendation applies to asymptomatic women. Women with known genetic mutations that increase their risk for ovarian cancer (for example, BRCA mutations) are not included in this recommendation.
Ovarian cancer has the highest mortality rate of all types of gynecologic cancer and is the fifth-leading cause of cancer death among women.
Although the mortality rate associated with ovarian cancer is high, the disease occurs infrequently in the general U.S. population, with an age-adjusted incidence of 13 cases per 100,000 women. As a result, the positive predictive value of screening for ovarian cancer—which directly depends on the prevalence of the disease—is low, and most women with a positive screening test result will have a false-positive result.
Benefits of Detection and Early Intervention and Treatment
The USPSTF found adequate evidence that annual screening with transvaginal ultrasonography and testing for a serum tumor marker, cancer antigen (CA)–125, in women does not reduce the number of ovarian cancer deaths.
Harms of Detection and Early Intervention and Treatment
Adequate evidence shows that screening for ovarian cancer can lead to important harms, including major surgical interventions in women who do not have cancer.
The USPSTF concludes that there is at least moderate certainty that the harms of screening for ovarian cancer outweigh the benefits.
Patient Population Under Consideration
This recommendation applies to asymptomatic women. Women with known genetic mutations that increase their risk for ovarian cancer (for example, BRCA mutations) are not included in this recommendation.
Women with BRCA1 and BRCA2 genetic mutations, the Lynch syndrome (hereditary nonpolyposis colon cancer), or a family history of ovarian cancer are at increased risk for ovarian cancer. Although no standardized referral criteria currently exist, women with an increased-risk family history should be considered for genetic counseling to further evaluate their potential risks. “Increased-risk family history” generally means having 2 or more first- or second-degree relatives with a history of ovarian cancer or a combination of breast and ovarian cancer; for women of Ashkenazi Jewish descent, it means having a first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer.
Women with a family history of ovarian cancer were not excluded from most randomized screening trials. In the only trial reporting ovarian cancer mortality results, women with a family history of ovarian or breast cancer comprised 17% of the participants. The overall trial showed no mortality benefit; outcomes were not separately reported for this subgroup. Although available evidence does not show with absolute certainty whether the balance of benefits and harms of ovarian cancer screening may differ for women with a family history of ovarian cancer, the USPSTF found no reason to believe that such women would necessarily benefit. A higher incidence of cancer may result in more diagnoses and treatments, but the increase may not be accompanied by a reduction in deaths and may actually lead to more associated harms. An ongoing prospective cohort study, the United Kingdom Familial Ovarian Cancer Screening Study, may help to resolve some of these questions.
Factors associated with a reduced risk for ovarian cancer include the use of oral contraceptives, pregnancy and breastfeeding, bilateral tubal ligation, and removal of the ovaries.
Transvaginal ultrasonography and serum CA-125 testing are readily available procedures and commonly suggested screening methods. The bimanual pelvic examination is often conducted (usually annually) in part to screen for ovarian cancer, although its effectiveness and harms are not well-known and were not a focus of this review.
The evaluation of abnormal test results consists of either repeated testing or, frequently, removal of one or both of the ovaries by means of laparoscopy or laparotomy.
Treatment of ovarian carcinoma includes surgical treatment (debulking) and intraperitoneal or systemic chemotherapy.
In its recommendation on genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility, the USPSTF recommends that women with a family history indicating that they are at risk for a deleterious mutation be referred for genetic counseling and testing. More information on this recommendation can be found at www.uspreventiveservicestaskforce.org.
In 2004, the USPSTF reviewed the evidence for screening for ovarian cancer and found that the potential harms outweighed the potential benefits of screening (1). A 2008 review of the literature commissioned by the USPSTF revealed no new evidence about the benefits of screening for ovarian cancer but provided some new data about observed harms of screening (2). In 2011, the USPSTF commissioned a bridge search to update the 2008 review, focusing on evidence available from randomized, controlled trials (3).
A single randomized, controlled trial, the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (4), has published mortality results associated with screening for ovarian cancer in asymptomatic, average-risk women using serum CA-125 testing (positive threshold of ≥35 kU/L [≥35 U/mL]) and transvaginal ultrasonography. In this trial, 78,216 women in the United States were randomly assigned to either annual screening (6 years for CA-125 testing and 4 years for transvaginal ultrasonography) or usual care and were followed for up to 13 years. Women were considered eligible if they were between 55 and 74 years of age and had no previous diagnosis of lung, colorectal, or ovarian cancer. Two initial exclusion criteria (previous oophorectomy and current tamoxifen use) were dropped during the recruitment phase. Nearly 90% of women were white, and 17% had a family history of breast or ovarian cancer. Management of abnormal test results was directed by the participant's personal health care provider. Although there was a nonstatistically significant finding of an increased number of ovarian cancer cases diagnosed in the screening group compared with the control group (212 vs. 176 cases; relative risk, 1.21 [95% CI, 0.99 to 1.48]), no difference was found in either stage at diagnosis or ovarian cancer death rate (118 vs. 100 deaths; relative risk, 1.18 [CI, 0.82 to 1.71]) (4). The low degree of contamination (<5%) and high rate of screening adherence (approximately 80%) seen during the trial, coupled with the lack of difference in stage at diagnosis, bolster the trial's finding that screening average-risk, asymptomatic women with serum CA-125 testing and transvaginal ultrasonography does not reduce ovarian cancer deaths.
Harms associated with screening for ovarian cancer have been reported by several trials. In the PLCO Cancer Screening Trial, approximately 10% of participants in the screening group received a false-positive result during the trial; the positive predictive value of CA-125 testing and transvaginal ultrasonography screening was just greater than 1% across all screening rounds (5). One third of women with a false-positive result had an oophorectomy, with an overall ratio of surgeries to screen-detected ovarian cancer of approximately 20:1. Nearly 21 major complications occurred per 100 surgical procedures done on the basis of false-positive screening results (4). A randomized trial set within the Shizuoka Cohort Study of Ovarian Cancer Screening evaluated the use of transvaginal or transabdominal ultrasonography in conjunction with serum CA-125 testing (positive threshold of >35 kU/L [>35 U/mL]) and reported that an estimated 33 surgeries were required to diagnose 1 case of screen-detected ovarian cancer (6).
An ongoing randomized trial, UKCTOCS (United Kingdom Collaborative Trial of Ovarian Cancer Screening), is evaluating the effect of annual screening with serum CA-125 testing and transvaginal ultrasonography follow-up for abnormal results, as determined by an ovarian cancer risk algorithm, taking into account age, absolute CA-125 level, and CA-125 trajectory over time, compared with annual screening with transvaginal ultrasonography or no screening. Data are available only from the pilot trial and the baseline (prevalence) screening round of the full trial. In the pilot, nearly 20% of women in the multimethod group who participated in the first screening were initially categorized as being at intermediate risk for ovarian cancer and required up to 5 additional blood tests before being returned to the low-risk pool. Less than 1% of participants had surgery to investigate an abnormal screening result (compared with approximately 2% in the PLCO Cancer Screening Trial); however, of the 16 women who had surgery, 11 (69%) did not have ovarian cancer (7). In the full trial, approximately 9% of women receiving baseline multimethod screening required repeated testing for abnormal results and less than 1% of women had surgery. Among women having surgery for a false-positive result (47 of 97 women [48%]), approximately 4% had a major complication (8).
No randomized trial has assessed the role of the bimanual pelvic examination for cancer screening. In the PLCO Cancer Screening Trial, bimanual examination was discontinued as a screening strategy in the intervention group because no cases of ovarian cancer were detected solely by this method and a high proportion of women had bimanual examination with ovarian palpation in the usual care group.
The USPSTF concludes that there is adequate evidence that there is no mortality benefit to routine screening for ovarian cancer with transvaginal ultrasonography or single-threshold serum CA-125 testing and that the harms of such screening are at least moderate. Final results from UKCTOCS should provide more information about the relative benefits and harms of an algorithm-based approach to screening for ovarian cancer.
Response to Public Comments
A draft version of this recommendation statement was posted for public comment on the USPSTF Web site from 10 April to 8 May 2012. In response to comments, the USPSTF clarified language describing what is meant by increased risk for ovarian cancer, what is known about ovarian cancer screening in women with a family history of the disease, and the diagnostic pathway for abnormal screening results.
Several commenters asked the USPSTF to provide information about other potential screening methods—in particular, a large panel biomarker screening test, OvaDx (Arrayit Corporation, Sunnyvale, California). The OvaDx test is not currently approved by the U.S. Food and Drug Administration for clinical use in ovarian cancer screening (it was submitted to the U.S. Food and Drug Administration for review in August 2010); pilot studies of its test characteristics are in progress (9). In the systematic evidence review commissioned by the USPSTF, which focused on randomized, controlled trials of screening with ovarian cancer morbidity or mortality as the outcomes of interest, no trials with these clinical outcomes were identified for any testing methods besides serum CA-125 testing and transvaginal ultrasonography, meaning that there is currently limited evidence to assess the ultimate health effects of other potential screening tests for ovarian cancer.
Commenters asked the USPSTF to include specific guidance or information about the potential role of symptoms in the earlier detection of ovarian cancer. The primary mission of the USPSTF is to make recommendations on clinical preventive services for average-risk persons without signs or symptoms of disease. As such, a search for data on the use of symptoms to guide detection of ovarian cancer was outside the scope of the commissioned systematic evidence review used to inform this recommendation statement. However, a literature search reveals that there is limited evidence available about the ultimate effectiveness of a combined symptoms-based approach with ancillary CA-125 testing or transvaginal ultrasonography; ovarian cancer morbidity and mortality were not specified or reported in available studies (10, 11). Symptoms included in the available studies were nonspecific in nature, including various gastrointestinal, urinary, gynecologic, and constitutional symptoms. Of note, 95% of women presenting to a primary care clinic report having at least 1 of these symptoms within the previous year, suggesting that there may be important inherent challenges related to the reliability of incorporating these nonspecific symptoms into ovarian cancer screening and diagnostic testing decisions (12).
Recommendations of Other Groups
Consensus among major medical and public health organizations is that screening for ovarian cancer in the general population is not recommended. The American Congress of Obstetricians and Gynecologists does not recommend screening for ovarian cancer in asymptomatic women; evaluation of high-risk persons may include transvaginal ultrasonography and CA-125 testing in addition to physical examination (13). The American Cancer Society states that there is no screening test proven to be effective and sufficiently accurate in the early detection of ovarian cancer. However, for women who are at high risk for ovarian cancer, the combination of a thorough pelvic examination, transvaginal ultrasonography, and a blood test for the tumor marker CA-125 may be offered (14).
Members of the U.S. Preventive Services Task Force
Members of the U.S. Preventive Services Task Force* at the time this recommendation was finalized are Virginia A. Moyer, MD, MPH, Chair (Baylor College of Medicine, Houston, Texas); Michael L. LeFevre, MD, MSPH, Co-Vice Chair (University of Missouri School of Medicine, Columbia, Missouri); Albert L. Siu, MD, MSPH, Co-Vice Chair (Mount Sinai School of Medicine, New York, New York; James J. Peters Veterans Affairs Medical Center, Bronx, New York); Linda Ciofu Baumann, PhD, RN (University of Wisconsin, Madison, Wisconsin); Kirsten Bibbins-Domingo, PhD, MD (University of California, San Francisco, San Francisco, California); Susan J. Curry, PhD (University of Iowa College of Public Health, Iowa City, Iowa); Mark Ebell, MD, MS (University of Georgia, Athens, Georgia); Glenn Flores, MD (University of Texas Southwestern, Dallas, Texas); Adelita Gonzales Cantu, RN, PhD (University of Texas Health Science Center, San Antonio, Texas); David C. Grossman, MD, MPH (Group Health Cooperative, Seattle, Washington); Jessica Herzstein, MD, MPH (Air Products, Allentown, Pennsylvania); Joy Melnikow, MD, MPH (University of California Davis, Sacramento, California); Wanda K. Nicholson, MD, MPH, MBA (University of North Carolina School of Medicine, Chapel Hill, North Carolina); Douglas K. Owens, MD, MS (Stanford University, Stanford, California); Carolina Reyes, MD, MPH (Virginia Hospital Center, Arlington, Virginia); and Timothy J. Wilt, MD, MPH (University of Minnesota Department of Medicine and Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota).
* For a list of current USPSTF members, go to http://www.uspreventiveservicestaskforce.org/members.htm.
1. Nelson HD, Westhoff C, Piepert J, Berg A. Screening for Ovarian Cancer: Brief Evidence Update. AHRQ Publication No. 04-0542-B. Rockville, MD: Agency for Healthcare Research and Quality; May 2004. Accessed at www.uspreventiveservicestaskforce.org/3rduspstf/ovariancan/ovcanup.htm on 30 August 2012.
2. Barton MB, Lin K. Screening for Ovarian Cancer: Evidence Update for the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement. AHRQ Publication No. 12-05165-EF3. Rockville, MD: Agency for Healthcare Research and Quality; April 2012. Accessed at www.uspreventiveservicestaskforce.org/uspstf12/ovarian/ovarart.htm on 30 August 2012.
3. Danforth KN, Im TM, Whitlock EP. Addendum to Screening for Ovarian Cancer: Evidence Update for the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement. AHRQ Publication No. 12-05165-EF4. Rockville, MD: Agency for Healthcare Research and Quality; April 2012. Accessed at www.uspreventiveservicestaskforce.org/uspstf12/ovarian/ovarartaddend.htm on 30 August 2012.
4. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, et al; PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening randomized controlled trial. JAMA. 2011;305:2295-303.
5. Partridge E, Kreimer AR, Greenlee RT, Williams C, Xu JL, Church TR, et al; PLCO Project Team. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol. 2009;113:775-82.
6. Kobayashi H, Yamada Y, Sado T, Sakata M, Yoshida S, Kawaguchi R, et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer. 2008;18:414-20.
7. Menon U, Skates SJ, Lewis S, Rosenthal AN, Rufford B, Sibley K, et al. Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol. 2005;23:7919-26.
8. Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009;10:327-40.
9. Arrayit Corporation announces premarket approval (PMA) submission strategy for OvaDx [Press release]. Sunnyvale, CA: Globe Newswire; 23 August 2010. Accessed at www.globenewswire.com/newsroom/news.html?d=199862 on 30 August 2012.
10. Rufford BD, Jacobs IJ, Menon U. Feasibility of screening for ovarian cancer using symptoms as selection criteria. BJOG. 2007;114:59-64.
11. Gilbert L, Basso O, Sampalis J, Karp I, Martins C, Feng J, et al; DOvE Study Group. Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol. 2012;13:285-91.
12. Goff BA, Mandel LS, Melancon CH, Muntz HG. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 2004;291:2705-12.
13. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice. Committee Opinion No. 477: the role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer. Obstet Gynecol. 2011;117:742-6.
14. American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society; 2012. Accessed at www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2012 on 30 August 2012.
Disclaimer: Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Financial Support: The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.
Potential Financial Conflicts of Interest: Disclosure forms from USPSTF members can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-2035.
Copyright and Source Information
This document is in the public domain within the United States.
Requests for Single Reprints: Reprints are available from the USPSTF Web site (www.uspreventiveservicestaskforce.org).
Source: This article was first published in Annals of Internal Medicine (Ann Intern Med 2012;11 Sep).
AHRQ Publication No. 12-05165-EF-2
Current as of September 2012
Screening for Ovarian Cancer: U.S. Preventive Services Task Force Reaffirmation Recommendation Statement. AHRQ Publication No. 12-05165-EF-2, September 2012. http://www.uspreventiveservicestaskforce.org/uspstf12/ovarian/ovarcancerrs.htm