Can a Urine Test Detect Deadly Prostate Cancer?

13 feb 2009--A new study suggests that a simple urine test may one day alert men to whether they have prostate cancer that can be ignored or must be aggressively treated.

Currently, a man must undergo a series of diagnostic tests, including a surgical biopsy, to confirm that he has prostate cancer. But no tests is able to determine reliably whether the cancer is slow-growing and probably nonfatal or aggressive and in need of immediate treatment. (Read " Halting Hormone Therapy Reduces Breast Cancer Risk Quickly.")

In the Feb. 11 edition of the journal Nature, however, a new study links specific molecules produced by the body to the aggressive form of the disease, suggesting that detecting these molecules could one day to lead to a reliable diagnosis and prognosis of prostate cancers.

Using new scanning and detection technology, scientists looked at over 1,000 metabolites - naturally occurring products of cell metabolism - and found that about 10 were often present in high levels in samples of blood, tissue and urine taken from patients with aggressive prostate cancer.

"This is proof-of-principle that we can identify metabolites...that might be correlated with aggressive prostate cancer versus slower-growing prostate cancer," Arul Chinnaiyan of University of Michigan Medical School, who led the study, said in a prepared statement.

Prostate cancer is the most common cancer among men in the developed world. In the U.S., where 186,000 Americans are diagnosed each year, only skin cancer is more common. But despite its prevalence, physicians have been frustrated by the lack of a fail-safe test. Currently, older men at risk of prostate cancer receive a PSA test, which detects a protein called prostate-specific antigen in the blood. Men who have elevated PSA levels, which may indicate cancer, undergo invasive biopsies, but often end up not having the disease at all. Even when the biopsy finds cancer, physicians are usually unable to tell accurately how quickly the cancer will spread.

"One of the main issues with prostate cancer is trying to distinguish aggressive prostate cancer that goes on to metastasize from the slow-growing version of the disease, and what we end up doing as physicians is over-treating our patients because we can't distinguish between them," Chinnaiyan says.

Given the risks and side effects of biopsies alone - which range from infection to impotence - an accurate diagnostic tool for physicians as straightforward as a urine test "would be, well, wonderful," according to Cory Abate-Shen, a professor at Columbia University College of Physicians and Surgeons, who authored a commentary accompanying the paper for Nature. "But that's something that will require large clinical trials to develop."

The Nature study focused on one particular metabolite, sarcosine, that was often found at elevated levels in samples taken from patients with advanced prostrate cancer, but was in lower levels in samples of healthy tissue. According to the study, scanning for sarcosine proved a more accurate mode of detection of cancer than even scanning for the PSA protein.

"We don't even know that sarcosine is the most promising metabolite," says Michael Shen, a professor at Columbia University College of Physicians and Surgeons who co-authored the Nature commentary with Abate-Shen, his wife. "It's the one they focused on. There are other metabolites identified in their study that could easily be as interesting or more interesting as sarcosine. So it would be very promising to look at the predictability of these individual metabolites but also their combination."

Warning that their work needed far more investigation, the researchers also raised the possibility that sarcosine could be a "therapeutic target," which might one day offer an effective treatment of the disease. In laboratory tests, they found that adding sarcosine to prostate cells caused benign cells to become cancerous and invasive. The researchers hope that drugs that stop sarcosine from working could effectively contain prostate cancers, and may even have implications for other cancer treatments.

In an interview with the Guardian newspaper, Christopher Beecher, a co-author of the study, said: "This is the molecule that the cancer cells use when they want to spread. If it turns out to be involved in metastasis in other cancers, then this discovery will be huge."