Ovarian Cancer Screening Is Not Recommended for Asymptomatic Women of Average Risk

Although the development of ovarian cancer (OC) is a relatively rare risk for US women, the disease is predominantly diagnosed in its later stages, decreasing prognostic favorability and leading to 14,000 deaths in the United States per year.¹ At present, there are no recommended screening tools for the general population. The available tests are reserved for women at high risk and still detect the disease in later stages. 

In 2018, the US Preventive Services Task Force issued a recommendation against screening asymptomatic women with no known high risk of OC. This recommendation was based on the task force’s literature survey, which found no appreciable decrease in mortality with current screening methods and also cited the potential for harm done from false-positive screening results.¹ The referenced screening tools consist of imaging and a biomarker blood test that are typically performed in tandem, as neither is considered sufficient alone.

The OC imaging modality most commonly used is transvaginal ultrasonography (TVUS), but screening can include other imaging modalities such as computed tomography (CT) and magnetic resonance imaging, as well as fluorodeoxyglucose-positron emission tomography/CT, and abdominal ultrasonography.² The American College of Radiology (ACR) issued its guidelines for use of imaging for OC screening in 2017 and did not support the use of imaging for screening those premenopausal and postmenopausal women considered to be of average risk (ie, women with no known personal or family history of OC and no genetic risk factors or biomarker cancer antigen [CA125] elevation). However, the ACR granted that some TVUS studies have shown encouraging results as a screening tool and that it might be considered for future use in conjunction with biomarkers for this purpose.²

As for those in the higher-risk premenopausal population, no randomized controlled studies have been reviewed that have found any decrease in mortality rate from imaging screening.² The ACR reported that despite current practices of TVUS screening of this population, OC continues to be diagnosed in its later stages.² The US Preventive Services Task Force reported that there have been some encouraging studies using TVUS as a screening tool. One such recent nested case-control study using pelvic ultrasound found that ultrasound-visualized complex cysts or solid masses were associated with an increased risk of OC, the diagnosis of which occurred at a mean of 3.4 months from the ultrasonography.³

In conjunction with ultrasonography, a blood test for the tumor biomarker CA125 is commonly performed. CA125 is increased in OC but is problematic in that it is a nonspecific tumor biomarker that is inconsistently expressed by OC tumors and by OC stage.^4,5 A UK study found no difference in mortality rate between those screened with CA125, TVUS, and those not screened.⁶ Hence, CA125 as a general screening tool is considered useful only when it is used in tandem with imaging.⁵

There is some promise for novel biomarkers or biomarker panels for preventive health screening in the future. Two studied biomarkers that could prove useful as part of a panel are human epididymis protein 4 (HE4) and lysophosphatidic acid (LPA). Elevations in HE4 have been found in two-thirds of early- and late-stage OC, but only in serous and endometrial epithelial OCs.⁵ LPA, on the other hand, was found to be expressed in 90% of stage I and in 100% of late-stage OCs. Furthermore, detected LPA levels corresponded with overall survival stage: later-stage OCs had higher levels of LPA expression. However, the use of LPA as a preventive screening tool may be limited, since it has also been detected in some healthy control patients and in patients with benign disease, which would better suit it for use in high-risk patient populations (to avoid false positives).⁵ In the meantime, research continues for screening biomarkers and tools that would enable diagnosis of OC in its earlier stages and, therefore, produce improved patient outcomes.

References

1. US Preventive Services Task Force. Grossman DC, Curry SJ, Owens DK, et al. Screening for ovarian cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(6):588-594.
2. Expert Panel on Women’s Imaging. Pandharipande PV, Lowry KP, Reinhold C, et al. ACR Appropriateness Criteria® ovarian cancer screening. J Am Coll Radiol. 2017;14(11S):S490-S499.
3. Smith-Bindman R, Poder L, Johnson E, Miglioretti DL. Risk of malignant ovarian cancer based on ultrasonography findings in a large unselected population. JAMA Intern Med. 2019;179(1):71-77.
4. Chandra A, Pius C, Nabeel M, et al. Ovarian cancer: current status and strategies for improving therapeutic outcomes. Cancer Med. 2019;8(16):7018-7031.
5. De La Franier B, Thompson M. Early stage detection and screening of ovarian cancer: a research opportunity and significant challenge for biosensor technology. Biosens Bioelectron. 2019;135:71-81.
6. Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240-1253.