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March 2008 Volume 2 #1
 Role of women in support groups New blood tests for PCa Physical activity and decreased PCa risk Conference 2008 • SUBSCRIBE • contact the editor • visit the cpcn website |
New blood tests for prostate cancer  The PSA test, which assesses the amount of prostate-specific antigen in the blood, has been for many years the gold standard blood test for alerting men to the possibility that they might have prostate cancer. But the test does have some drawbacks. Other conditions, such as aging and benign prostatic hyperplasia (BPH), increase the levels of PSA in the blood and lead to "false positives" --- men thinking they might have prostate cancer when they don't. On the other hand, the PSA test sometimes misses cases of cancer, a worrying possibility called a "false negative." (See an archived article from April 2005 on the topic of false positives.)So researchers in Canada and around the world have been busy trying to come up with a better blood test for prostate cancer. Early prostate cancer antigen-2 (EPCA-2) One promising discovery, first reported about a year ago, is EPCA-2. Dr. Robert Getzenberg of the James Buchanan Brady Urological Institute at Johns Hopkins is the lead author of a small retrospective study on using this blood protein to test for prostate cancer. 
The study, which appeared in the April 2007 issue of Urology, looked at the EPCA-2 levels in the blood of 330 Hopkins patients. The men studied had various medical histories: normal PSA levels and no evidence of the disease, high PSA levels and normal biopsies, a diagnosis of BPH, normal PSA levels yet a diagnosis of prostate cancer, prostate cancer confined to the prostate, prostate cancer that had spread outside the prostate at the time of surgery, and various other benign conditions.Getzenberg and his team found that the EPCA-2 test was negative in 97 percent of the men who did not have prostate cancer. Besides this, men with no evidence of prostate cancer during digital rectal exams (regardless of their PSA levels), as well as men suffering from other types of cancer or from benign conditions, all had EPCA-2 levels below the one that researchers used as a cut-off --- 30 nanograms per millilitre. A press release from Johns Hopkins compares these findings with the results of a multi-institutional study published in 2003 in the Journal of Urology, which found that PSA levels between 4 and 10 nanograms per millilitre were accurate in identifying patients without prostate cancer only 19 percent of the time. (See this press release.) Research is ongoing and still promising. Getzenberg reported in May 2007 that expanded studies continue to demonstrate that early prostate cancer antigen-2 (EPCA-2) has high sensitivity and specificity. (In non-clinical language, a sensitive test detects almost all cases of prostate cancer --- few false negatives. And a specific test detects prostate cancer almost exclusively --- few false positives.) According to Dr. Getzenberg, "A blood test based on EPCA-2 may greatly improve our ability to accurately detect prostate cancer early and minimize the number of false positives, therefore lowering the number of unnecessary biopsies." The other possible use of EPCA-2 is in distinguishing between men whose prostate cancer is confined to the prostate and those whose cancer has spread. EPCA-2 levels, says Dr. Getzenberg, seem to be much better than PSA levels at separating these two groups of men. (Listen to a Urological Times interview of Dr. Getzenberg at the 102nd Scientific Meeting of the American Urological Association.) Still, it is really too early to tell whether EPCA-2 testing will work better than the traditional methods of diagnosing prostate cancer. The initial Johns Hopkins study, while promising, was retrospective (meaning it tested men whose cancer status was already known), and it was small. In other words, it did not reproduce the conditions under which the PSA test is currently used, so accurate comparisons are difficult. It should also be noted that Dr. Getzenberg holds a patent on the test and has consulted for and received a grant from Onconome, a Seattle biotech company developing EPCA-2 as a commercial product. The prestigious National Cancer Institute also supports Dr. Getzenberg's EPCA-2 research, and larger clinical trials are underway. Preliminary results may be available as early as the end of 2008. Gene-variant testing for prostate cancer risk A second study, published in the February 28 issue of the New England Journal of Medicine, looked at the DNA of 2,893 Swedish men with prostate cancer and 1,781 healthy men of similar ages to determine whether men with single-nucleotide polymorphisms (SNPs) in five particular areas of their DNA had an increased risk of developing prostate cancer. A SNP (pronounced "snip") is a genetic variation --- a change in the DNA sequence --- that occurs when one single nucleotide (A, T, C, or G) is altered. Although many SNPs have no effect on cell function, researchers think that some of these genetic variations predispose people to diseases and influence responses to particular drugs. In this case, researchers looked at 16 SNPs from 5 regions of the chromosomes in all of the men. They found that 5 of these SNPs were more common in the men who had prostate cancer. When they looked at these 5 specific SNPs individually, they found that each was associated with prostate cancer, but only moderately. But it was a different picture when men had more than one of these SNPs --- the more of these SNPs the higher the likelihood that the man had prostate cancer. Men with a family history of the disease and the 5 SNPs accounted for about 46 percent of the cases of prostate cancer in the Swedish men that were studied. The researchers also calculated that men with five risk factors or more had an odds ratio for prostate cancer of 9.46. (A family history of the disease is equal to one risk factor as is each SNP.) Dr. David Penson warns in a Medscape Urology interview about these findings that an odds ratio is not the same as relative risk, so "you can't say [about men with 5 or more risk factors] that they're 9 times more likely to develop cancer than men who don't have the 5 ... but they're clearly at much greater risk." Three other studies published in the February 10 online edition of Nature Genetics consider prostate cancer risk and genetic variations. Research teams from the United Kingdom, the United States, and Iceland, working independently, uncovered at least 10 new genetic variations associated with an increased risk for prostate cancer. One of these studies, lead by Dr. Julius Gudmundsson of deCODE Genetics Corp. in Iceland, found that a particular genetic variation (2p15) is strongly associated with the risk of developing an aggressive form of prostate cancer. According to Dr. Durado Brooks, director of prostate and colorectal cancers at the American Cancer Society, "This is the sort of information that has the potential to be most useful in the clinical setting." Although investigating the connection between genetic variations and the risk of developing prostate cancer does add to our knowledge of the disease, some worry that genetic testing of this sort may do as much harm as good. "Technology today enables us to find out a huge amount of information," says Dr. Gelmann of Columbia University's cancer centre. "But how does the public deal with this information? How does it help them make decisions? And, if they make a decision, does that lead to a day, a week, a month, of life saved?" Still, the genetic genie is out of the bottle and unlikely to get stuffed back in. The researchers who published the January 2008 article have already founded the company Proactive Genomics, which is making its Focus5TM prostate cancer risk test available for about $300. Not far behind were the researchers from deCODE, who now offer deCODE ProCaTM a $500 test of eight known genetic variants associated with prostate cancer risk. For more information on assessing your prostate cancer risk, visit CPCN's article "Who is at risk for developing prostate cancer?" |
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