Prostate cancer : Noninvasive urine test moves a step closer

Researchers have identified a unique molecular signature of prostate cancer in urine. This may pave the way for an accurate, noninvasive test for the condition.
The scientists — from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, MD — used RNA and other molecules in urine to differentiate between males with prostate cancer and those with nonmalignant prostate conditions or healthy prostates.

Prostate cancer is the second most common cancer among males in the United States, after skin cancer. Around 1 in 9 males will receive a diagnosis of this condition in their lifetime.

In the U.S. alone, almost 192,000 males will receive a diagnosis in 2020, and over 33,000 will die from the condition.

Flawed tests
Prostate cancer is highly treatable, especially if a doctor diagnoses it early. However, there are often no symptoms in the early stages, and existing screening tests are problematic.

For example, the widely used prostate-specific antigen (PSA) blood test is unreliable, giving a lot of false-positive results and not discriminating benign from aggressive forms of cancer.

As part of a regular health check, or if a male’s PSA levels are elevated, a doctor may perform a digital rectal examination (DRE). However, these tend to be quite invasive, which discourages many males from undergoing them.

Doctors recommend a biopsy if they find anything suspicious during a DRE. However, even a biopsy cannot provide a definitive test, and the procedure can be painful.

“A simple and noninvasive urine test for prostate cancer would be a significant step forward in diagnosis,” says senior study author Ranjan Perera. The study now appears in the journal Scientific Reports.

“Tissue biopsies are invasive and notoriously difficult because they often miss cancer cells, and existing tests, such as PSA […] elevation, are not very helpful in identifying cancer.”

According to the National Cancer Institute, only about 25% of males who undergo a biopsy following a positive PSA test actually have prostate cancer.

Dislodged cells
Male urine contains a small amount of cells shed from different parts of the urinary tract, including the prostate. Scientists can isolate, process, and analyze these cells using various molecular techniques.

Existing prostate urine tests involve a health professional first massaging the prostate to dislodge more of these cells. However, recent research suggests that this may be unnecessary. Indeed, males may actually be able to collect urine samples at home and mail them to a laboratory for testing.

For the new study, the researchers recruited 126 males. Of these, 64 had prostate cancer, 31 had nonmalignant prostate conditions (benign prostatic hyperplasia or prostatitis), and 31 had no cancer. They collected urine samples without first massaging the prostate.

Cells become cancerous partly as a result of genetic and metabolic changes that provide the energy boost they need to proliferate rapidly.

To identify a unique molecular signature of these changes in prostate cancer, the researchers sequenced RNA molecules and used mass spectrometry to measure metabolites in the samples.

“We discovered cancer-specific changes in urinary RNAs and metabolites that — if confirmed in a larger, separate group of patients — will allow us to develop a urinary test for prostate cancer in the future.”

– First study author Bongyong Lee, of Johns Hopkins All Children’s Hospital in St. Petersburg, FL

Unlike the PSA test, the RNA and metabolite profile that the researchers identified could distinguish between males with prostate cancer and those with nonmalignant prostate conditions.

The scientists write in their paper that a test based on their findings could also determine how advanced a cancer is.

However, they emphasize that this was a proof-of-principle study. Larger studies are necessary to validate the test before it is ready for clinical use.

They say that in the future, their findings might inspire new treatments for the condition based on the metabolic changes they identified.

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