Draft Recommendation Statement
Ovarian Cancer: Screening
This opportunity for public comment expired on August 14, 2017 at 8:00 PM EST
Note: This is a Draft Recommendation Statement. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF. The final Recommendation Statement will be developed after careful consideration of the feedback received and will include both the Research Plan and Evidence Review as a basis.
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.
Draft: Recommendation Summary
The USPSTF recommends against screening for ovarian cancer in asymptomatic women.
This recommendation does not apply to women who are known carriers of genetic mutations that increase their risk for ovarian cancer (e.g., BRCA1 or BRCA2 gene mutations).
The US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious 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.
The age-adjusted incidence of ovarian cancer from 2010 to 2014 was 11.4 cases per 100,000 women per year.1 It is the fifth most common cause of cancer death among women.1 More than 95% of ovarian cancer deaths occur among women age 45 years and older.2
The positive predictive value of screening for ovarian cancer is low, and most women with a positive screening test result do not have ovarian cancer (i.e., they receive a false-positive result).
Benefits of Screening
The USPSTF found adequate evidence that screening with transvaginal ultrasound, testing for the serum tumor marker cancer antigen (CA)–125, or a combination of both does not reduce the number of deaths from ovarian cancer in women.
Harms of Screening
The USPSTF found adequate evidence that screening for ovarian cancer in asymptomatic women not at high risk can result in important harms, including many false-positive results, which can lead to surgical interventions in women who do not have cancer. Depending on the type of screening test used, the magnitude of harm ranges from moderate to substantial, and reflects the risk of unnecessary surgery. The USPSTF found inadequate evidence on the psychological harms of screening for ovarian cancer.
The USPSTF concludes that there is at least moderate certainty that the harms of screening for ovarian cancer outweigh the benefits.
Draft: Clinical Considerations
Patient Population Under Consideration
This recommendation applies to asymptomatic women. This recommendation does not apply to women who are known carriers of genetic mutations that substantially increase their risk for ovarian cancer (e.g., BRCA1 or BRCA2 gene mutations or Lynch, Li-Fraumeni, or Peutz-Jeghers syndrome).
Women with high-risk genetic syndromes, including BRCA1 and BRCA2 gene mutations, Lynch syndrome (hereditary nonpolyposis colon cancer), Li-Fraumeni syndrome, and Peutz-Jeghers syndrome, are at high risk for ovarian cancer. Women with a family history of ovarian cancer are also at increased risk.3, 4
Most randomized screening trials reviewed by the USPSTF did not exclude women with a family history of ovarian cancer.3 In the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 1.6% of participants reported a maternal history of ovarian cancer and 6.4% reported a family history of breast cancer5; in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, 17.4% of participants reported a family history of breast or ovarian cancer in any first-degree relative.6 Although available evidence does not show with absolute certainty if the balance of benefits and harms of screening for ovarian cancer differs for women with a family history of ovarian cancer, the USPSTF found no reason to believe that such women would necessarily benefit from screening. A higher incidence of cancer may result in more diagnoses and treatment, but these increases may not result in a reduction in deaths, and could even potentially lead to more associated harms.
The clinical symptoms of ovarian cancer are nonspecific and often present at later stages of disease; therefore, use of clinical symptoms for risk stratification for the early detection of disease is difficult.
Although the USPSTF does not recommend routine screening, transvaginal ultrasound and serum CA-125 testing are readily available procedures and commonly suggested screening methods. In a separate recommendation statement, the USPSTF found insufficient evidence to determine the balance of benefits and harms of performing screening pelvic examination to detect a range of gynecologic conditions, including ovarian cancer, in asymptomatic women.7
The evaluation of abnormal test results consists of repeat testing with the same or a different test and often surgical removal (by laparoscopy or laparotomy) of one or both of the ovaries and fallopian tubes. Diagnostic guidelines suggest surgical removal of the complete ovary or ovaries, rather than tissue biopsy, to confirm the diagnosis of ovarian cancer.
Treatment of ovarian cancer typically includes surgical treatment (debulking) and intraperitoneal or systemic chemotherapy.
In a separate recommendation statement, the USPSTF recommends that women with a family history indicating that they are at risk for a deleterious gene mutation (BRCA1 or BRCA2) be referred for genetic counseling and, if indicated, genetic testing.8 The USPSTF also concluded in a separate recommendation statement that the current evidence was insufficient to assess the balance of benefits and harms of performing screening pelvic examination in asymptomatic, nonpregnant adult women.7
Draft: Other Considerations
Research Needs and Gaps
Given that most cases of ovarian cancer are diagnosed at later stages, when associated mortality is high, further research is needed to identify new screening strategies that could accurately detect ovarian cancer earlier, at a point when outcomes could be improved. Given the potential for serious harms from diagnostic workup of positive screening results (i.e., surgical removal of the ovary), new screening strategies should minimize false-positive results and be highly specific. Additionally, studies evaluating the benefits and harms of using these screening strategies in asymptomatic women not at increased risk for ovarian cancer are needed. Study outcomes should include ovarian cancer mortality, surgery rates, surgical complication rates, and psychological harms.
Burden of Disease
From 2010 to 2014, ovarian cancer was the eighth most common cancer in the United States and the fifth most common cause of death from any cancer.1 In 2017, it is estimated that 22,440 new cases of ovarian cancer will be diagnosed in the United States and 14,080 deaths will occur.9 Early stages of the disease are often asymptomatic. Symptoms are usually nonspecific and can include abdominal pain or pressure, bloating, constipation, urinary symptoms, back pain, or fatigue.10 The majority of women (88%) diagnosed with ovarian cancer are older than age 45 years, with a median age at diagnosis of 63 years.2 Most women with ovarian cancer are diagnosed at later stages; approximately 60% of women have distant spread of disease at the time of diagnosis.2 In 2014, white women had the highest diagnosis rate (11.3 cases per 100,000 women), followed by Hispanic women (10.0 cases per 100,000 women), Asian/Pacific Islander women (9.0 cases per 100,000 women), black women (8.7 cases per 100,000 women), and American Indian/Alaska Native women (6.8 cases per 100,000 women). White women are most likely to die of ovarian cancer, followed by black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native women.1 Women with the following features in their family history are at increased risk of ovarian cancer: a family history of ovarian cancer; a family history of BRCA1 or BRAC2 genetic mutation; a family history of Lynch, Li-Fraumeni, or Peutz-Jeghers syndrome4; two or more first- or second-degree relatives with a history of ovarian cancer or a combination of breast and ovarian cancer; and, in women of Ashkenazi Jewish descent, one first-degree relative (or two second-degree relatives on the same side of the family) with breast or ovarian cancer.
Mortality rates from ovarian cancer vary by stage at diagnosis; 5-year survival rates by stage at diagnosis range from 92.5% for localized cancer to 28.9% for cancer with distant spread.11
Scope of Review
The USPSTF commissioned a review of the evidence on screening for ovarian cancer to update its 2012 recommendation. The evidence review focused on evaluating the benefits and harms of screening for ovarian cancer in asymptomatic, average-risk women. Outcomes of interest included ovarian cancer mortality, quality of life, false-positive rate, surgery and surgical complication rates, and psychological effects of screening. Any screening approach that was evaluated by clinical trial design was included.
Effectiveness of Screening
The USPSTF reviewed direct evidence evaluating the benefits of screening for ovarian cancer on mortality.3 The USPSTF identified three good-quality studies evaluating the effect of annual screening in asymptomatic women not known to be at high risk for ovarian cancer. None of the studies found that screening significantly reduced ovarian cancer mortality. The largest and most recent trial, UKCTOCS, was a randomized, controlled trial of 202,638 postmenopausal women ages 50 to 74 years.5 More than 95% of trial participants were white; 1.6% reported a maternal history of ovarian cancer and 6.4% reported a maternal history of breast cancer. The trial evaluated the effects of two screening strategies, transvaginal ultrasound or CA-125 testing with the Risk of Ovarian Cancer Algorithm® (ROCA) (Abcodia, Inc., Boston), which evaluates changes in CA-125 values over time, following a baseline age-adjusted measurement. Women randomized to the transvaginal ultrasound arm had annual screening with transvaginal ultrasound, while women randomized to the CA-125 ROCA arm had annual CA-125 testing with ROCA. Women found to be at increased risk for ovarian cancer based on ROCA were then screened with transvaginal ultrasound. Women in the control arm received no screening. After a median followup of 11.1 years, ovarian cancer mortality (including peritoneal and fallopian tube cancer) was similar in the control and intervention arms (0.35%, 0.32%, and 0.32% in the control, transvaginal ultrasound, and CA-125 ROCA arms, respectively). The primary trial results found no significant difference in mortality (transvaginal ultrasound arm: hazard ratio, 0.91 [95% confidence interval (CI), 0.76 to 1.09]; CA-25 ROCA arm: hazard ratio, 0.89 [95% CI, 0.74 to 1.08]).3, 5 The pilot trial for UKCTOCS, UK Pilot, was much smaller (n=21,955 randomized). It evaluated the use of a single cutpoint value for CA-125 testing and found no significant difference in ovarian cancer mortality between women who were screened versus not screened (0.08% vs. 0.16%; relative risk, 0.5 [95% CI, 0.22 to 1.11]).3, 12
The only trial conducted in the United States was the PLCO trial. In this trial, 78,216 women were randomly assigned to either annual screening (CA-125 testing and transvaginal ultrasound for the first four rounds of screening, then CA-125 testing only for an additional two rounds) or usual care; median followup was 12.4 years. Women were considered eligible if they were ages 55 to 74 years and had no previous diagnosis of lung, colorectal, or ovarian cancer. Nearly 90% of women were white, and 17.4% of participants had a family history of breast or ovarian cancer. Abnormal test results were managed by the participant's personal health care provider. No difference was found in ovarian cancer mortality (0.34% in the screening arm vs. 0.29% in the usual care arm; relative risk, 1.18 [95% CI, 0.82 to 1.71]).3, 6
Potential Harms of Screening
The USPSTF reviewed evidence on harms of screening for ovarian cancer from the three studies described above, as well as a fourth fair-quality study reporting on quality of life and psychological harms of screening (Quality of life, Education, and Screening Trial [QUEST]) (n=549 analyzed).13 Calculated false-positive rates of the various screening methods were: 4.2% in the UK Pilot trial, using a single cutpoint value for CA-125 testing (excluding peritoneal cancer); 11.9% in the UKCTOCS trial, in the first round of screening with transvaginal ultrasound (excluding peritoneal cancer); 9.0% in the UKCTOCS trial, in the first round of screening with CA-125 ROCA (excluding peritoneal cancer); and 44.2% in the UKCTOCS trial, in all subsequent rounds of screening with CA-125 ROCA.3 In the PLCO trial, the calculated false-positive rate of screening with CA-125 and transvaginal ultrasound was 9.6%.3 Among women randomized to screening, across the trials, the percentage who ultimately had surgery due to a false-positive test result ranged from 0.2% to 3.2%. Major surgical complications occurred in 0% to 15% of these women.3
The USPSTF reviewed evidence on the psychological harms of screening for ovarian cancer from the UKCTOCS and QUEST trials.3, 5, 13, 14 The UKCTOCS trial measured anxiety using the State-Trait Anxiety Inventory and the 12-item General Health Questionnaire in a subset of participants. Although no significant differences were found between the intervention and control arms, there was a greater odds of psychological morbidity among women who were referred to higher levels of screening.14 The QUEST trial evaluated the effect of screening for ovarian cancer on cancer worry and quality of life (as measured by the modified Cancer Worry Scale, the Impact of Event Scale, and the mental and physical health scores of the 36-item Short-Form Health Survey) among average-risk U.S. women age 30 years and older. Cancer screening consisted of alternating CA-125 testing and transvaginal ultrasound every 6 months, for a maximum of four screening rounds. The trial found that women with abnormal test results were more likely to report cancer worry at 2 years of followup (odds ratio, 2.8 [95% CI, 1.1 to 7.2]) than women without abnormal results.13
Estimate of Magnitude of Net Benefit
The USPSTF found adequate evidence that screening for ovarian cancer does not reduce ovarian cancer mortality in asymptomatic women not at high risk for ovarian cancer. Three large, good-quality studies all found no benefit in ovarian cancer mortality from annual screening in asymptomatic women not at high risk for ovarian cancer. The USPSTF also found adequate evidence that the harms from screening for ovarian cancer are at least moderate, and may be substantial in some cases. Harms from screening for ovarian cancer include false-positive results, which may lead to diagnostic surgery, often resulting in removal of one or both of the ovaries and fallopian tubes. Serious surgical complications can also result. Given the lack of mortality benefit seen with screening in asymptomatic, average-risk women, and the moderate to substantial harms that could result from screening, the USPSTF concludes with moderate certainty that the harms of screening for ovarian cancer with CA-125 testing (either using a single cutpoint or with ROCA), transvaginal ultrasound, or a combination of both outweigh the benefit, and the net balance of the benefit and harms of screening is negative.
Draft: Update of Previous USPSTF Recommendation
This recommendation statement is consistent with the 2012 USPSTF recommendation. Since 2012, the large UKCTOCS trial was published, which confirmed the PLCO trial's finding that screening for ovarian cancer does not decrease deaths from ovarian cancer in asymptomatic women not known to be at high risk for ovarian cancer.
Draft: Recommendations of Others
There is consensus among major medical and public health organizations that screening for ovarian cancer in the general population is not recommended. The American College of Obstetricians and Gynecologists does not recommend screening for ovarian cancer in low-risk, asymptomatic women; evaluation of high-risk women may include transvaginal ultrasound and CA-125 testing, in addition to physical examination.15 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 ultrasound, and the CA-125 blood test may be offered.9 The American College of Radiology does not recommend screening for ovarian cancer in women at average risk.16 The American Academy of Family Physicians recommended against screening for ovarian cancer in women in 201217; currently, it is in the process of reviewing this recommendation.
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16. Protocol for the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Version 7.1. https://www.ucl.ac.uk/womens-health/research/womens-cancer/gynaecological-cancer-research-centre/ukctocs/files/ukctocs_protocol71. 2015. Accessed December 19, 2017.
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18. Pinsky PF, Yu K, Kramer BS, et al. Extended mortality results for ovarian cancer screening in the PLCO trial with median 15 years follow-up. Gynecol Oncol. 2016;143(2):270-5.
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20. Barrett J, Jenkins V, Farewell V, et al; UKCTOCS Trialists. Psychological morbidity associated with ovarian cancer screening: results from more than 23,000 women in the randomised trial of ovarian cancer screening (UKCTOCS). BJOG. 2014;121(9):1071-9.
21. U.S. Preventive Services Task Force. Screening for ovarian cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2012;157(12):900-4.
22. Committee on Gynecologic Practice. Committee Opinion No. 716: the role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer. Obstet Gynecol. 2017;130(3):e146-e149.
23. Smith RA, Andrews KS, Brooks D, et al. Cancer screening in the United States, 2017: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2017;67(2):100-21.
24. Brown DL, Andreotti RF, Lee SI, et al. ACR appropriateness criteria© ovarian cancer screening. Ultrasound Q. 2010;26(4):219-23.
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26. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version I. Fort Washington, PA: NCCN; 2017.
Internet Citation: Draft Recommendation Statement: Ovarian Cancer: Screening. U.S. Preventive Services Task Force. February 2018.