Investigational assay detects the fusion of two genes that occurs in about half of prostate cancers.

ORLANDO—A urine test may enable clinicians to predict which men diagnosed with prostate cancer are more likely to have aggressive disease and which men might benefit most from androgen deprivation therapy (ADT).

Researchers at Gen-Probe Incorporated, San Diego, have developed a prototype molecular assay called the T2:ERG urine test, which detects the fusion of two genes: TMPRSS2 and ERG. This fusion is found in about half of all prostate cancers and has been associated with more aggressive disease.

Continue Reading

“The T2:ERG urine test showed high specificity for detection of prostate cancer at biopsy,” said lead author Jack Groskopf, PhD, Director of Research and Development at Gen-Probe’s Cancer Diagnostics Division.

“We also found that TMPRSS2-ERG fusion messenger RNA (mRNA) levels correlated with indicators of prognosis. These preliminary data suggest that the test could be used, along with other clinical information, to help distinguish which men can be monitored and which require more aggressive treatment, an invaluable tool for physicians.”

Dr. Groskopf, who presented the latest data on the test at the 2009 Genitourinary Cancers Symposium here, said widespread use of PSA testing has resulted in high rates of early prostate cancer detection, although many early-stage prostate tumors are unlikely to become life-threatening.

The PSA test is not useful for distinguishing between men who need aggressive treatment and those who can be placed on active surveillance. The low specificity of the PSA test can result in high false-positive rates and unnecessary biopsies, he noted.

He and his colleagues prospectively analyzed TMPRSS2-ERG fusion mRNA levels in urine specimens from 556 men scheduled for prostate biopsy. Those results were then correlated with biopsy outcome. All patients were treated at three hospitals in California, Michigan, and Quebec.

The biopsies showed that 226 of the men (41%) had prostate cancer. The new urine test predicted the presence of cancer at biopsy with a specificity of 85%. By comparison, the PSA test has a specificity of 27%, according to the researchers.

TMPRSS2-ERG fusions were detected in 42% of the men with prostate cancer, a number that indicates high sensitivity because previous studies have found that about 50% of men with prostate cancer have the gene fusion.

Moreover, the T2:ERG urine test correlated with criteria currently used to identify aggressive cancer at the time of biopsy: Gleason score, percentage of biopsy cores that tested positive for cancer, and the amount of cancer found in the biopsy specimen.

The researchers also noted that because the gene fusion provides an explanation, at the molecular level, for the dependence of prostate tumors on certain hormones, such as testosterone, the T2:ERG urine test may be useful for determining which men would respond best to ADT.

“We have some very promising initial data, but we are continuing clinical research studies to define the optimal clinical utility and assay format,” Dr.Groskopf told Renal & Urology News. “We believe this gene fusion urine test is going to help with probably the greatest unmet need in prostate cancer diagnostics: discriminating so-called significant from indolent cancers.”

Eric A. Klein, MD, chairman of the Glickman Urological & Kidney Institute and professor of surgery at Cleveland Clinic in Ohio, said this is interesting work that could significantly help improve the management of prostate cancer over the next two to three years.

“This will add to our ability to determine whether or not a person with a specific PSA level actually has cancer,” Dr. Klein said. “So, if a patient who is 55 years old has a PSA of 4 ng/mL and last year it was 2.5, do you biopsy him or not? We don’t know the answer because PSA is prostate-specific but not prostate cancer-specific.”