Because ovarian cancer is usually diagnosed at an advanced stage—when prognosis is much worse than earlier in its course—a great deal of effort has been directed toward developing strategies to detect it early. These strategies include screening by a woman’s primary gynecologist with 1) a test of the serum CA-125 level and 2) transvaginal ultrasonography (TVU).
But how useful are the results of those screening tests? How should they be interpreted?
The answers aren’t clear.
Recent studies have yielded new information about ovarian cancer screening and detection. We discuss them in this Update:
- Screening with serial testing of the CA-125 level and TVU still is not recommended by the US Preventive Services Task Force or by ACOG
- Initial preliminary data from a prevalence screen of more than 50,000 subjects in the United Kingdom are encouraging, and show that new screening strategies may be feasible
- Using a patient’s report of her symptoms to trigger medical evaluation for ovarian cancer is not an effective screening tool
- Women who have an adnexal mass and a serum CA-125 level >35 U/mL and abnormal sonographic findings have an increased likelihood of ovarian cancer. They should be referred directly to a specialist.
The effect of screening on ovarian cancer mortality remains unknown
Partridge E, Greenlee RT, Xu J-L, et al. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol. 2009;113(4):775–782.
The potential benefit of an effective screening program for ovarian cancer is great; the disease is the most lethal of all common gynecologic malignancies and carries significant individual and societal costs.1 Furthermore, diagnosis at an early stage is associated with improved survival.
To date, however, studies have not shed light on whether screening with CA-125 testing or TVU has an impact on morbidity or mortality from ovarian cancer. In a large, multicenter trial of more than 30,000 women, Partridge and colleagues attempted to answer this question.
Investigators sought to determine whether this cohort of healthy women, ranging in age from 55 to 74 years, experienced a reduction in mortality from ovarian cancer when subjects were screened annually with a combination of CA-125 testing and TVU. The study was part of a larger trial (the Prostate, Lung, Colorectal and Ovarian [PLCO] Cancer Screening Trial2).
Subjects were randomized 1:1 to 1) the screening arm or 2) their customary gynecologic care without screening. The regimen in the screening arm comprised:
- annual measurement of the CA-125 in Years 1 through 6
- annual TVU in Years 1 through 4
- evaluation and follow-up of positive screening tests at the discretion of each subject’s treating physician.
Distribution of staging was unaffected. Overall, the positive predictive value of the screening regimen was relatively constant—and quite low—across the screening years (1.1% in Year 1 [95% confidence interval (CI), 0.6–1.6]; 1.0% in Year 2 [95% CI, 0.4–1.5]; 1.1% in Year 3 [95% CI, 0.5–1.7]; and 1.3% in Year 4 [95% CI, 0.6–2.0]).
Of 3,388 women who had at least one positive result on either screening test, 1,170 (34.5%) underwent biopsy at some point. Of those, 60 (5.1%) had invasive cancer—yielding a surgery-to-detected-cancer ratio of 19.5:1.
Approximately 70% of cancers detected by screening were a Stage-III or -IV tumor. As such, the screening effort did not change the expected distribution of staging from what would be expected in an unscreened population.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Do not yet screen your general patient population for ovarian cancer with combined annual CA-125 testing and transvaginal ultrasonography. Determination of whether screening with this strategy will reduce mortality from ovarian cancer must await the final results of the larger PLCO trial.
Is it feasible to screen for ovarian cancer on a large scale?
Menon U, Gentry-Maharaj A, Hallett R, 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(4):327–340.
The low prevalence of ovarian cancer presents a significant challenge to anyone hoping to devise a useful screening program: A screening test designed to detect a low-prevalence disease must have exceptionally high sensitivity and specificity to achieve a clinically useful positive predictive value—especially when the intervention is relatively risky (surgical removal of the ovaries) and has known harmful health implications.