Doctors Seek New ëGold Standardí For Prostate Cancer Detection by Gina Shaw For years, the ìgold standardî for prostate cancer screening has been a test for something called prostate-specific antigen (PSA), a marker that doctors have long used as an indicator of prostate cancer risk. Elevated levels of PSA, a substance produced by normal prostate glands, are thought to point to an increased risk of prostate cancer, the most common cancer in men. About one in every six men will develop prostate cancer over the course of a lifetime. ìWhen prostate cancer develops, the PSA level usually goes above four [nanograms per millimeter],î say patient education materials from the American Cancer Society, which recommends that men 50 and over have a yearly PSA screening. According to the organization, if your level is above four, but less than 10, you have about a 25 percent chance of having prostate cancer. If it goes above 10, your chance of having prostate cancer is over 50 percent and increases further as your PSA level increases. So far, so good. But the ìgold standardî test is showing some tarnish. For some time now, there have been questions about the reliability of PSA as a prostate cancer predictor; screenings tend to have a lot of false positives. In January, researchers at Stanford University published the results of a study that showed elevated PSA levels donít necessarily predict canceróoften, they are nothing more than a reflection of harmless increases in prostate size, known as benign prostate hyperplasia. ìProstate cancer is being overdiagnosed and overtreated because of the misconception that PSA is primarily a reflection of prostate cancer,î said Dr. Thomas Stamey, a Stanford urology professor and lead author of the study, which appeared in The Journal of Urology. ìProstate cancer, like all other cancers, cannot be detected at an early stage by a blood test,î said Stamey. ìWhat we need is a new marker.î As with other cancers, hope for just such a reliable marker has come from genetic analysis. Researchers at several leading medical centers, including the University of Massachusetts, Johns Hopkins and the University of Michigan, have recently identified a gene that, when prostate cancer is present, overproduces a protein called AMACR (a-methylacyl-CoA racemase). An enzyme that helps to metabolize fat, AMACR hadnít been previously linked to any type of cancer, but it now appears to be one of the most consistent biological markers for prostate cancer that has ever been foundómore than 95 percent of prostate tumors analyzed by the Hopkins researchers showed overexpression of the AMACR gene. Michigan scientists got much the same results. The protein doesnít necessarily cause prostate cancer, but it appears to be consistently present in cancer cells. ìThe beauty of AMACR is that it is cancer-specific and found only in malignant cells,î said Dr. Mark A. Rubin, an associate professor of pathology and surgery at University of Michiganís medical school and one of the lead authors of a study on AMACR, published in the April 3 edition of the Journal of the American Medical Association. ìPSA canít differentiate between cell changes caused by cancer and those caused by benign changes in the prostate.î At present, this ìblindnessî in the PSAís results, and the resulting false positives, can lead to repeated biopsies, unnecessary surgery and, of course, panicked patients. But donít expect to find doctors advising an annual AMACR screening for men over 50 just yet. Currently, testing for AMACR involves inserting a needle into the prostateóa more invasive process than the simple PSA blood test. Still, itís potentially useful for doctors facing a questionable prostate biopsy, which happens about 15 percent to 20 percent of the time. The next step, say scientists, is to find out whether signs of an overactive AMACR gene can be found in the blood, and if so, to develop a blood test for it. In fact, AMACR could also aid in the diagnosis of other types of cancer as well. The Michigan scientists found increased levels of the protein in cells from cancers that included colorectal, lymphoma, melanoma, ovarian, breast, bladder, lung and renal cell cancer. Along with prostate, AMACR levels were highest in colorectal cancer. The new genetic marker doesnít mean that the PSA test is obsolete. Researchers such as Rubin believe that a combination of PSA and AMACR testing could provide the most accurate screening system for prostate canceróand, in theory, eliminate the need for prostate needle biopsies altogether. For the 189,000 men who will be diagnosed with prostate cancer in the United States this yearóand for the millions of others who worry about itóthe promise of more accurate early detection is good news. Gina Shaw is the medical writer for The Washington Diplomat.