Academic OB/GYN

Our first reader question –

“A patient of mine had ovarian cancer, she’s brought her 13 year old in for a consultation regarding various issues of irregular menses. ….how soon we should start getting CA125s…. Have an answer/opinion for exactly how young to start?”

That’s a great question!

First, there is probably not a definitive answer.  Screening for ovarian cancer is clearly an area where we do not have good answers.  I think a clear part of this question is actually whether or not the patient should be screened at all.  Patients think that there should be a good screening for ovarian cancer, but based on current literature and practice, I don’t think there is any method for screening this patient that is effective.

Per American Cancer Society as of 8/27/09:

“The problem with this test is that conditions other than cancer can also cause high levels of CA-125. In addition, someone with ovarian cancer can still have a normal CA-125 level. When a CA-125 level is abnormal, many doctors will repeat the test (to make sure the result is correct). The doctor may also consider ordering a transvaginal ultrasound test. In studies of women at average risk of ovarian cancer, these screening tests did not lower the number of deaths caused by ovarian cancer. This is why transvaginal sonography and the CA-125 blood test are not recommended for ovarian cancer screening of women without known strong risk factors. Even when these tests are used in women at high risk, it is not known how helpful they are.” (http://bit.ly/mayII)

I think the issue with screening this patient is that there are so many reasons a young person could have a positive CA125, it is unclear what one would do with the result.  Some have suggested that one could get serial CA125 tests and look for an escalating level, which would make sense, though I don’t believe this has been evaluated prospectively.

Several studies have shown CA125 screening to be ineffective even in BRCA+ positive women, even in combination with serial transvaginal scanning.  These patients have as high as 50% chance of getting ovarian cancer, while the patient you describe (assuming no other family history) has only a 5% lifetime risk.

Stirling et al “Annual surveillance by transvaginal ultrasound scanning and serum CA-125 measurement in women at increased familial risk of ovarian cancer is ineffective in detecting tumors at a sufficiently early stage to influence prognosis.”

Olivier et al “By combining CA125 with TVU results, a PPV of 40% was achieved. However, the diagnostic tools appear to be only sensitive in detecting ovarian cancer at an advanced stage, while three of four tumors with early-stage disease in this series had normal screening tests prior to the diagnosis.”

That being said, there are a few studies that have shown some more promising results…

Tailor et al “Transvaginal sonography can effectively detect intraovarian cancer and tumors of borderline malignancy in women with a family history of the disease. Screening efficacy is related to the type of family history.”

I think the best answer is that there is no clear benefit to screening this patient.   It would be worthwhile to get BRCA testing on the mother, which if positive, would have clear implications for the daughter.  If the daughter were BRCA positive she would be candidate for prophylactic oopherectomy after she completes childbearing.  A genetic counseling visit for the mother and daughter would be appropriate, and can help guide decision making.   New information is coming out all the time on this topic, and genetic counselors are often very up to date.  Your referral gyn/oncologist may also have a good opinion.

She also can reduce her lifetime risk of ovarian cancer by using birth control pills except when she desires pregnancy.  If she is strongly interested in screening, there may be a screening research protocol ongoing at a nearby academic center.

Sources:

Screening for familial ovarian cancer: failure of current protocols to detect ovarian cancer at an early stage according to international Federation of Gynecolgoy and Obstetrics System.Stirling D, Evans DG, et al.  J Clin Oncol. 2005 Aug 20;23(24):5588-96.

Screening for familial ovarian cancer: poor survival of BRCA 1/2 related cancers. Evans DG, Gaarenstroom KN et al. J Med Genet. 2009 Sep;46(9):593-7. Epub 2008 Apr 15.

CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Olivier RI, Lubsen-Brandsma MA. Gynecol Oncol. 2006 Jan;100(1):20-6. Epub 2005 Sep 26.

Results from an ultrasound-based familial ovarian cancer screening clinic: a 10-year observational study. Tailor A, Bourne TH et al.  Ultrasound Obstet Gynecol. 2003 Apr;21(4):378-85.

Thanks for the question!  Hope that helps a bit

Nicholas Fogelson, MD