Genetic testing to guide prostate removal: too soon to know if it helps

By Daniel Pendick

Is it possible for a gene test to identify whether a prostate that’s healthy today is sure to develop cancer down the road? And should results of such a test be the basis for removing a seemingly healthy prostate gland? Those are questions raised by recent press reports of a British man who had his prostate gland removed because he carried a faulty gene called BRCA2. The 53-year-old man was taking part in a prostate cancer trial conducted by the Institute of Cancer Research.

Genetic testing has been used to guide cancer treatment for several years. But it reached a new height when actress Angelina Jolie revealed in The New York Times that she had both of her breasts removed. She did this not because she had breast cancer, but because she carried a gene called BRCA1 that put her at high risk of developing breast cancer in her lifetime. Jolie wasn’t the first woman to do this, but was certainly the most famous one so far.

Although press reports likened the British man’s decision to Jolie’s, it’s important that men understand that the comparison is not entirely valid.

For one thing, removal of the man’s prostate was not purely preventive, because a biopsy had already shown the presence of very early prostate cancer. He also had a family history of prostate and breast cancer, further raising his risk above that of the average man. Under these circumstances, many men in the United States—and their doctors—might have considered treatment, whether or not they had the BRCA mutations or not.

Jolie, in contrast, made her decision to have both breasts removed based solely on her BRCA gene status. No biopsy had shown the presence of early stage breast cancer.

BRCA1 and BRCA2

BRCA1 and BRCA2 belong to a class of genes known as tumor suppressors. They make proteins that somehow suppress the birth or survival of cancer cells. These genes were discovered in hereditary BReast CAncer cells, which is how they got their names. Since then, mutations in the BRCA1 and BRCA2 genes have also been linked to a variety of other cancers, including ovarian, cervical, uterine, pancreatic, testicular, and prostate cancers. (You can learn more about BRCA1 and BRAC2 at the National Cancer Institute’s website.)

Results from an international clinical trial published earlier this year in the Journal of Clinical Oncology found that men with the BRCA2 gene mutation are more likely to develop aggressive and fatal prostate cancers.

Should testing for BRCA2 guide whether a man have his prostate removed? Although it isn’t currently the sole piece of evidence, it may contribute to the decision making process. “In the setting of a strong family history, this could be one additional data point used to arrive at a decision,” says Dr. Marc B. Garnick, clinical professor of medicine at Harvard-affiliated Beth Israel Deaconess Medical Center in Boston, and editor of the Harvard Medical School Annual Report on Prostate Diseases. “But we are nowhere near providing any definitive answers on this question in 2013.”

Trying to predict the development of cancer before it happens is still in its infancy. No one knows if identification of a BRCA mutation followed by prostate removal prevents death and disability. “If a man decides to undergo prostatectomy or other treatment due to the possibility of developing prostate cancer suggested by a BRCA test, there are absolutely no viable data to support such a decision,” Dr. Garnick says. “We need to study this in greater depth to understand the risks and benefits of such an approach.”

Such early detection is especially problematic for prostate cancer. Many older men—perhaps the majority of them—have some cancer cells in their prostate glands. But these cells tend to grow so slowly that they never threaten health or longevity. If methods to eliminate cancer cells, such as removing the prostate or killing cancer cells with radiation, were completely safe and effective, then early warning would make sense. But they aren’t.  Treatment can cause erectile dysfunction, incontinence, and others problems. These must be weighed against the hypothetical benefit of “preventive” treatment.

Someday, a simple blood test may identify men who almost certainly will have the kind of prostate cancer that could turn deadly. Until then, BRCA testing should be just one piece of evidence used to guide treatment.

Daniel Pendick is the executive editor of the Harvard Men’s Health Watch.