HERA Expert Answers Questions about CA125

June 30, 2014

Many women have questions about the CA125 blood test as it relates to ovarian cancer.  HERA Board member and medical advisor, Sarah Adams, explains what the CA125 test measures, outlines the symptoms of ovarian cancer, and discusses the importance of getting a second opinion if a woman  knows something isn’t “right.”

Sarah Adams

Can you help us understand why the CA125 is a good screening tool for some, but not for everyone?

CA125 is a protein which is elevated in the blood of some women with ovarian cancer.  It can be measured with a simple blood test, and levels correlate with response to therapy in women undergoing treatment.  CA125 levels are also measured after completion of cancer treatment to monitor for disease recurrence.

In addition to using CA125 levels as a surrogate marker for tumor burden in women with a confirmed ovarian cancer diagnosis, many clinicians have used CA125 levels to evaluate women with ovarian masses to determine how likely it is that the mass is a cancer, and some clinicians measure CA125 levels in women at high risk of ovarian cancer as a way of screening for the disease.

Unfortunately, because CA125 levels can be elevated in benign conditions (endometriosis, fibroids, infections), and because as many as 50% of women with early-stage ovarian cancer do not have elevations in their CA125 levels, this test is not sensitive or specific enough to recommend for screening in the general population.  In fact, following the results of a trial that enrolled 78,237 women between the ages of 55 and 74 who were randomized to annual screening (four years of transvaginal ultrasounds and six years of CA125 serum levels) or usual care which failed to show a difference in ovarian cancer-specific or overall mortality, the US Preventative Task Force has recommended against screening average-risk women for ovarian cancer, stating that screening can cause more harm than benefit.  This is because the only way to confirm a cancer diagnosis is to remove the ovary surgically, and many women from the trial who underwent surgery but were not diagnosed with cancer had complications as a result of their operations.

Importantly, the recommendations against surgery by the USPTF do not apply to women at high risk of ovarian cancer, including women with a strong family history of breast or ovarian cancer, or women who have been tested and found to carry a genetic mutation that increases their risk of developing ovarian cancer (BRCA1 or BRCA2 mutations, or women with Lynch Syndrome).  In these women, the National Comprehensive Cancer Network (NCCN) and the American College of Obstetricians and Gynecologists (ACOG) recommend that physicians measure CA125 levels every 6 – 12 months and obtain a transvaginal ultrasound to screen patients for ovarian cancer.  This testing should start at age 30-35 or 5-10 years before the earliest diagnosis in a family member.  Despite these recommendations, ACOG states that there is no evidence that screening improves survival in women high-risk populations, and the NCCN finds there is not sufficient evidence to support screening for ovarian cancer in any population, including women at increased risk.

It is also important to recognize that the USPTF recommendations against screening do not apply to women with symptoms of ovarian cancer who are seeking a diagnosis or treatment.  In patients with a pelvic mass or abnormal findings on exam, a CA125 elevation may prompt referral to a cancer specialist.

If there is no screening for ovarian cancer how is it ever diagnosed?

It can be difficult to make a diagnosis of ovarian cancer because the most common symptoms experienced by women are vague, and are usually not present until the tumor has already spread within the abdominal cavity.  The four most common symptoms reported by women who were diagnosed with ovarian cancer are: 1) abdominal bloating or increased abdominal girth; 2) pelvic pain; 3) changes in bowel or bladder habits; 4) loss of appetite or quickly feeling full.  Because these symptoms may also be present in patients with gastrointestinal disorders,  a diagnosis of ovarian cancer may not be considered initially by patients or clinicians.  To educate both health care professionals and the public about these symptoms and the importance of early referral to gynecologic oncologists for the treatment of ovarian cancer, education campaigns with the slogan “Ovarian Cancer:  It whispers!”  have been launched.

Ultimately, a diagnosis of ovarian cancer requires surgery to remove the ovary, or part of the ovary.  This operation should be performed by a gynecologic oncologist or by an experienced pelvic surgeon in consultation with a gynecologic oncologist, since multiple studies have shown that outcomes are better among women treated by specialists in ovarian cancer.

If someone experiences the symptoms of ovarian cancer, what should she do?

If a woman has pelvic pain, persistent bloating, and increase in her abdominal girth, changes in her bowel or bladder habits, or early satiety, she should consult with her physician and ask whether these might be symptoms of an ovarian cancer.  To evaluate her, the clinician would most likely perform a physical exam – including a pelvic exam – and may order blood tests (CA125) or imaging studies (CT or ultrasound).  Based on the results of these procedures, a woman may be referred to a gynecologic oncologist for further work-up or treatment.

What if her doctor tells her that everything is fine but she knows something isn’t “right”?

Documenting the frequency and quality of symptoms can help a physician to make a diagnosis.  Discussing symptoms that may be concerning for ovarian cancer with a gynecologist or a primary care physician may also be helpful.  In any case, it is always appropriate to seek a second opinion for any medical concern.

What can one of our readers do to help?

Getting the word out about the symptoms of ovarian cancer may help women get appropriate care and surgery faster.  In addition, despite numerous studies by researchers all over the world, there is still no effective screening test for ovarian cancer.  Helping to fund innovative research through organizations like HERA may change this.   We know that the cure rate for women diagnosed with ovarian cancer while it is still confined to the ovaries exceeds 90%, but the overall survival rate is only 40% because we so rarely find this cancer early.   Diagnosing this cancer before it has a chance to spread – in most cases before it has even caused symptoms – would be expected to radically alter the outcomes for the thousands of women diagnosed each year and is the most important priority for ovarian cancer research.

Sarah Adams, MD, is an Assistant Professor of Gynecologic Oncology at the University of New Mexico in Albuquerque.

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