Tag Archives: ovarian cancer

Ovarian Cancer CA-125 Blood Test: Does It Work?

Stephanie Portes-Antoine, Brandel France de Bravo, MPH, and Laura Gottschalk, PhD, Cancer Prevention and Treatment Fund

Ovarian cancer is a deadly disease because it is rarely diagnosed early. There is not yet an effective, life-saving screening tool for the early diagnosis of ovarian cancer.

When ovarian cancer is diagnosed in the early stage—before the cancer has spread beyond the ovaries—chances of a woman’s survival are very good, with about 93% of women surviving at least 5 years.  Unfortunately, only 15% of cases are caught this early, because the symptoms of ovarian cancer are not obvious. For women diagnosed with advanced ovarian cancer, the chances of 5-year survival drop to less than 30%.[1] Given the dramatic differences in survival outcomes between advanced and early onset diagnosis, it is vitally important to detect ovarian cancer early.

Most women whose ovarian cancer is detected in the late stages will have a relapse (usually many times) following their initial treatment, requiring additional treatment.[2] The most widely used test to screen for the recurrence of ovarian cancer is the CA-125. This blood test measures a protein that tends to be higher in women with ovarian cancer. The test was approved for use on women who have already been diagnosed with ovarian cancer once. In 2008, Dr. Vladimir Nosov from UCLA Medical Center and his co-authors reported that elevated levels of the CA-125 biomarker are found in approximately 83% of women with advanced stage ovarian cancer and 50% of patients with stage I disease.[3]

Is testing for this “biomarker” an effective way to tell early on if a woman’s ovarian cancer has returned? And what about women who have never been diagnosed with ovarian cancer? Why can’t the CA-125 test be used to screen them?

Women with No Symptoms or Who Have Never Been Diagnosed with Ovarian Cancer

Other studies have confirmed that CA-125 by itself is not sensitive enough to diagnose ovarian cancer in the very early stage of the disease, before there are symptoms. Dr. Saundra S. Buys is co-director of the Family Cancer Assessment Clinic at the Huntsman Cancer Institute in Salt Lake City, Utah. According to Dr. Buys, CA125 testing “may be appropriate to screen for ovarian cancer in women who have abdominal symptoms, but for women who have no medical symptoms, doing screening for ovarian cancer results in a lot of false-positives.”[4] False positives are test results that inaccurately show the person might have cancer. Dr. Buys based her conclusions on data for women ages 55 to 75 who were participating in a large study called the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.[5]

In 2011, Dr. Buys and her colleagues published more results from that trial which involved more than 78,000 women. They concluded that using the CA-125 blood test to screen for ovarian cancer doesn’t prevent women from dying from the disease, it actually is harmful.[6] False positives resulted in many women having unnecessary surgery: 3,285 women received false positives and 1080 of these women underwent biopsy surgery. In 15% of cases, the unnecessary surgery caused serious complications. At the same time, there was no benefit in terms of survival for the women who took the test as compared with those who did not.

Women Who Have Previously Had Ovarian Cancer

CA-125 by itself is clearly not reliable at detecting early ovarian cancer in women of low or average risk—women who have never before been diagnosed with ovarian cancer, and women who have no symptoms. Is it at least effective at detecting a recurrence of ovarian cancer?  In 2010, Dr. Gordon Rustin of the Mount Vernon Cancer Centre in England published the results of a study done with women who had already been diagnosed with and treated for ovarian cancer. He found  that women who started chemotherapy early, based on a CA125 test result indicating relapse of ovarian cancer, did not live any longer than women who did not begin treatment until symptoms of relapse appeared.[7]

The Future of Ovarian Cancer Screening

Research is underway to evaluate whether the CA-125 test can be used more reliably, either by administering it only to women with other biomarkers that indicate increased risk (such as elevated levels of the protein HE4) or combined with other screening tests such as vaginal ultrasound.

Dr. Karen Lu from the MD Anderson Center at the University of Texas has had success correctly identifying postmenopausal women at high risk for ovarian cancer by measuring CA-125 at regular intervals and relying on a mathematical model. Only women whose CA-125 levels went up over time were given a vaginal ultrasound, and only those with suspicious findings on the ultrasound had surgery. This two-staged approach seemed potentially effective .[8] However, when this approach was studied on more than 200,00 women, it did not significantly prevent death from ovarian cancer.[9]

The Bottom Line:

The CA-125 test by itself is not a good screening tool for ovarian cancer. When used alone on women with no symptoms or previous history of ovarian cancer, it leads to many false positives. Among women who have already been treated for ovarian cancer once, it doesn’t seem to matter whether they get treatment for their ovarian cancer recurrence based on CA-125 results or based on their symptoms. Either way, women who relapsed and got treatment lived about the same amount of time.

References:

  1. The National Cancer Institute. Surveillance Epidemiology and End Results. SEER Stat Fact Sheets. Cancer: Ovary. http://seer.cancer.gov/statfacts/html/ovary.html
  2. NCI Cancer Bulletin. Early Chemo to Prevent Ovarian Cancer Recurrence Fails to Increase Survival. June 2, 2009. Volume 6/Number 11. http://www.cancer.gov/ncicancerbulletin/060209/page2
  3. Nosov V., et al. The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125? American Journal of Obstetrics and Gynecology. September 2008: 199(3): 215-223.
  4. Reinberg, S. Ovarian screening Methods Inaccurate. National Women’s Health Resource Center. November 7, 2005. http://www.healthywomen.org/resources/womenshealthinthenews/dbhealthnews/ovariancancerscreeningmethodsinaccurate
  5. Buys S.S., et al. Ovarian cancer screening in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial: Findings from the initial screening of a randomized trial. American Journal of Obstetrics and Gynecology. November 2005: 193(5): 1630-1639.
  6. Buys S.S., et al. Effects of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. The Journal of the American Medical Association. July 2011; 2011 (616):1.
  7. Rustin, G.J. and van der Burg. Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomized trial. Lancet. October 2010
  8. Lu, Karen et al. A 2-Stage Ovarian Cancer Screening Strategy Using the Risk of Ovarian Cancer Algorithm (ROCA) Identifies Early-Stage Incident Cancers and Demonstrates High Positive Predictive Value. Cancer. September 2013; 2013 (119):17.
  9. Jacobs  IJ, Menon  U, Ryan  A,  et al.  Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial . Lancet. doi:10.1016/S0140-6736(15)01224-6.

Choosing wisely: tests and treatments cancer patients usually DON’T need

By Jennifer Yttri, PhD
2013

The thought of cancer is so frightening that many patients depend on their physicians to make all the decisions about screening, prevention, and treatment.  Or they may ask for whatever “new cure” they have heard about.  That can result in too many tests or treatments that do more harm than good.  Not every test, procedure, or medication is appropriate for every patient, and many are over-used. What is beneficial for one person isn’t worth the risks for another.

The best health decisions can be made when physicians take the time to talk with their patients and patients ask questions rather than just assuming the doctor always knows best.

The ABIM Foundation and Consumer Reports collaborated with specialty medical societies to create lists of “5 Things Physicians and Patients Should Question” as part of a national effort called Choosing Wisely (www.choosingwisely.org). These medical groups represent more than 500,000 physicians. The lists contain evidence-based recommendations made by experts. Here is the list of their recommendations on cancer.

Breast cancer screening

Breast cancer screening is done through mammograms, which are like x-rays.  A breast cancer diagnosis involves giving the cancer a stage (0 through 4, with 4 being the most advanced) based on the size of the tumor, how advanced it is, and how likely it is to spread. Other imaging tests, like PET, CT, and bone scans are not recommended for screening early stage breast cancer (stages 0-3), patients newly diagnosed with Ductal Carcinoma In Situ (DCIS), or people without symptoms. This testing does not benefit patients, and false-positives (test results that indicate cancer when no cancer is present) can lead to unnecessary procedures and misdiagnosis. For anyone who has been treated for early-stage breast cancer and is symptom free, mammograms and regular clinical exams are the best ways to check that the cancer has not come back.  Advanced imaging tests and tumor marker tests should only be used for patients with later-stage breast cancer.

Cancer therapy

The first round of cancer therapy works best at reducing or eliminating a tumor. Multiple treatments, including chemotherapy, will not always help get rid of cancer, especially more advanced cancers or tumors that return. After three different treatments, another round is unlikely to improve quality or length of life. It is better to stop therapy and not suffer through the side effects of treatment.  (In fact, there is some evidence that patients live longer, with better quality of life, if they stop aggressive treatments earlier.)

Cervical cancer screening

Women over 65 should stop being screened for cervical cancer if they have not previously shown risk for disease. Women under 30 should not have HPV tests to screen for cervical cancer. Women with mild dysplasia or cervical intraepithelial neoplasia (CIN1) for less than two years should not be treated for cervical cancer, as CIN1 is usually caused by a short-term HPV infection and goes away within a year.   See below for information about HPV testing. Pap smears should be used to screen for cervical cancer.

Colon cancer screening

For people who are at an average risk for developing colon cancer, tests such as stool tests and sigmoidoscopy can be used instead of colonoscopy to screen for colon cancer. Abnormal results from these tests require follow-up with a colonoscopy. The plasma test named methylated Septin 9 (SEPT9) is an alternative screening test but it is not recommended unless the more conventional tests and colonoscopy are not feasible.

HPV testing

HPV testing is not recommended for low risk infections, such as for HPV associated with genital warts. HPV testing should be used to identify high risk infections in patients with abnormal Pap smears or other clinical symptoms associated with high risk HPV infections.

Ovarian cancer screening

Women at average risk who do not have symptoms should not be screened for ovarian cancer. Screening using ultrasound or blood serum testing might detect early signs of cancer, but ovarian cancer is uncommon in women of average risk without symptoms. An abnormal result that isn’t cancer might require invasive follow-up, and those risks outweigh the benefit of early detection.

Ovarian cysts

Small, simple cysts are common in women and usually won’t affect their health. If one is found, the doctor will schedule an ultrasound to determine if the cyst is benign (not cancer). If the cyst is not cancerous, a follow up ultrasound and surgery is not recommended unless the cyst causes symptoms, like pelvic pain. If the cyst is suspected to be cancerous, a follow up ultrasound is not recommended because the cyst should just be surgically removed.  A second ultrasound is only recommended for larger cysts that the doctor could not be sure about.

Palliative care for bone metastasis

Cancers that spread to bones are often very painful. Local radiation is sometimes used to treat patients with one or a few bone metastases, but some doctors question if the increased risk of cancer warrants radiation as treatment for pain. The American Society for Radiation Oncology recommends using one dose of radiation to relieve pain from any bone metastasis. While another dose might be needed in the future, starting with one dose makes sense, since patients with bone cancer have a short life expectancy.

Prostate cancer screening

Men who do not have symptoms generally should not be screened for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam as it can lead to treatments that may do more harm than good. Gleason and prostate-specific antigen (PSA) tests are used to measure how aggressive prostate cancer is and how likely it is to spread. Imaging tests can then be performed to identify exactly where cancer has spread. These imaging tests, such as bone scans, PET, and CT, are not recommended for detecting disease in men who are newly diagnosed with low-grade prostate cancer. Imaging tests are expensive, can expose men to high levels of radiation, and are unlikely to provide more information about early prostate cancer. Only men with Gleason scores above 7 and PSA levels above 10 nanograms/mL should consider imaging tests.

Prostate specific antigen (PSA)

High PSA levels may be a sign of prostate cancer. However, having a low PSA level does not prevent prostate cancer nor does it mean there is no cancer. It was thought that antibiotics might lower PSA and protect men from prostate cancer. This has not been proven in clinical tests and is not recommended as an alternative preventive therapy.

Stage 1 non-small cell lung cancer (NSCLC)

Lung cancer is the most common type of cancer to spread to the brain. However, the chance of patients with Stage 1 lung cancer developing brain metastasis is very low. Because of the rate of false positives is much higher than the actual rate of brain metastasis, brain imaging by MRI or CT is not recommended for patients with stage 1 NSCLC unless they have neurologic symptoms.

Thyroid scans

Radioactive iodine is absorbed by the thyroid and can be used to give doctors a picture of what the thyroid looks like, how it is functioning, and if there are any nodules in the area. Imaging with radioactive iodine is not recommended for determining whether thyroid nodules are benign or cancerous unless the patient is hyperthyroid. Nodules should be biopsied if the thyroid functions normally.