The Big C is now the title of a show, but the term is one that has always been the source of great fear. Many of my patients come in to the office asking to be screened for ovarian cancer. If you have a family history of ovarian cancer, multiple relatives with breast and/or colon cancer, or you had early breast cancer, especially if you are of Ashkenazi Jewish origin, screening is indeed in order. In these circumstances, I suggest a special genetic blood test for BRCA1 and BRCA2 mutations. (The BRCA stands for breast cancer, but these mutations increase risk of breast and ovarian cancer.) If a BRCA mutation is found, screening may not suffice…the current recommendation is that a woman who has a high genetic risk for ovarian cancer undergo ovarian removal (bilateral oophorectomy) subsequent to completing childbearing or by the age of 40. And because of her high risk for breast cancer she should consider whether to undergo prophylactic mastectomy or follow-up for breast cancer with yearly MRI’s. Of course, most women will have neither a high-risk history nor this type of genetic mutation…they are considered “average-risk” But the fear of ovarian cancer remains meaningful for all of us. It is the fifth leading cause of cancer deaths in women…partly because it is usually diagnosed at an advanced stage.
The symptoms of ovarian cancer are very nonspecific and common; most of us have experienced some of them. They include bladder irritation with frequency and urgency, bloating and abdominal distention (and most of us feel that way when we try on old jeans), unexplained weight loss, decreased appetite and and/or fatigue. These symptoms usually occur late in the disease. If ovarian cancer is found while just confined to the ovary, 5-year survival is 92%. Unfortunately when it is found at an advanced stage (spread to other organs in the pelvis or metastasized in other areas of the body) the 5-year survival is only 30%. So it makes sense that if we could screen for this cancer and find it before it spread, the prognosis would greatly improve. This hypothesis was tested in the Prostate, Lung, Colorectal and Ovarian (PLOC) Cancer Screening Trial. The results of the evaluation of two screening tools, transvaginal ultrasound and a blood test of serum cancer antigen 125 (CA-125) were reported in the June 2011 issue of JAMA.
The trial followed 78,216 women at average risk for ovarian cancer between the ages of 55 and 74. They were followed at 10 screening centers in the United States from 1993 to 2001. The trial was done with proper randomization. Half of the women were offered screening with a baseline transvaginal ultrasound, which was repeated annually over an additional 3 years as well as a baseline CA-125 blood test followed by an annual blood test for an additional 5 years. The other half of the women were not offered these tests but received “usual” medical care. The women’s physicians received all the test results and then decided how to interpret and manage them. The participants were followed for a maximum of 13 years for cancer diagnosis and death until February 2010. (I know that’s over a year ago, but it takes time to gather and analyze the data.)
Here are the results: Ovarian cancer was diagnosed in 212 women in the intervention group and 176 in the usual care group. There were 118 deaths caused by the ovarian cancer in the intervention group and 100 deaths in the usual care group (The statisticians then translated this to 3.1 deaths per 1000 person-women years in the intervention group and a slightly lower 2.6 deaths per 1000 person- years in the usual care group.) But get this…. 3285 of the screened women had false positive results (i.e. either the CA-125 was elevated or there was a suspicious mass on their ultrasound). Of these, 1080 of the women underwent surgery to follow-up on the results and 163 experienced at least 1 serious complication (that’s 15% of those who had “unnecessary” surgery). Deaths from other causes (excluding ovarian, colorectal, and lung cancer) were essentially the same in both groups (2924 in the screened women and 2912 in those not screened). There was also no “stage shift”. In other words, screening did not make a difference as to whether the cancer was found at an early or late stage. (I’ll spare you the numbers here….. I know they are becoming cumbersome.)
The conclusion by the researchers and authors was that “annual screening for ovarian cancer as performed in the PLCO trial with simultaneous CA-125 and transvaginal ultrasound does not reduce disease-specific mortality in women of average risk for ovarian cancer but does increase invasive medical procedures and associated harms.” In other words: There was no advantage to screening, and in some cases it resulted in harm.
There will be additional studies coming out of Europe in which lower thresholds of the CA 125 blood test are used for initial screening (perhaps it will be more sensitive); but there is no doubt that we need a new and better way to detect ovarian cancer at an early stage. Researchers are working on it…I’ll try to keep you posted when you see me and online.