Novel Urinary Assay Improves Prostate Cancer Detection

SAN FRANCISCO — A new urinary assay for a common gene rearrangement in prostate cancer improves the detection of this disease and the differentiation of its more aggressive forms, according to two cohort studies reported at a symposium on genitourinary cancers.

The studies, conducted among men who were scheduled for prostate biopsy or prostatectomy, found that the assay supplemented conventional risk factors for accurately identifying those having prostate cancer. In addition, higher assay scores correlated with the presence of adverse tumor features.

Dr. John T. Wei presented results of the first study on behalf of Sheila M.J. Aubin, Ph.D., of Gen-Probe Inc., the company that is developing the assay.

Prostate-specific antigen (PSA) level and digital rectal examination both have poor specificity for detecting prostate cancer. Moreover, these tests are unable to differentiate indolent from aggressive cancer, said the professor of urology at the University of Michigan in Ann Arbor.

About half of prostate cancers exhibit fusion of the androgen-regulated TMPRSS2 gene and the ERG oncogene. Cancers that harbor this fusion gene (abbreviated T2:ERG) have increased cell growth, invasion, and metastasis, and decreased apoptosis, Dr. Wei said at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

In the first study, the investigators assessed the performance of the novel assay, which measures levels of T2:ERG messenger RNA in urine, using urine specimens collected after digital rectal examination and before either prostate biopsy (623 men) or prostatectomy (142 men).

Analyses of biopsy-based indicators showed that the T2:ERG score was correlated with the number of cores that were positive, the percentage of cores that were positive, and the greatest percentage involvement of any core by cancer, according to Dr. Wei. Also, the median score was higher among patients with biopsy-significant cancer as defined by Epstein criteria.

Analyses of prostatectomy-based indicators showed that the T2:ERG score was correlated with the maximum tumor dimension. In addition, the median score was higher among patients who had an upgrade of the Gleason score between biopsy and prostatectomy, a prostatectomy Gleason score of greater than 6, and prostatectomy-significant cancer as defined from tumor characteristics.

Compared with the PCPT (Prostate Cancer Prevention Trial) risk score alone, the combination of this score with the T2:ERG score more accurately identified men who had prostate cancer (area under the curve, 0.75 vs. 0.65).

Dr. Wei noted that at cutoff scores of 100 and 200, the T2:ERG assay had high specificity for distinguishing between patients with and without cancer (88%–93%), with biopsy-significant and -insignificant cancer (85%–95%), and with prostatectomy-significant and -insignificant cancer (95%–100%).

Independent trials of the assay are needed, Dr. Wei acknowledged.

In the second study, investigators tested the same T2:ERG assay using urine specimens that were collected after digital rectal examination from 471 men who were scheduled for prostate cancer biopsy at community clinics, according to Dr. James B. Amberson.

Some 44% of patients had positive biopsies, he reported. The median age was 66 years in the patients with cancer and 63 years in the patients without it. The median serum PSA level was 5.0 and 4.3 ng/mL, respectively.

When used alone, the T2:ERG score had a high specificity (87%) for detection of biopsy-proven cancer, reported Dr. Amberson, divisional medical director of Dianon Systems Inc., the manufacturer of another test that was also used in the study. Sensitivity was 39%.

The median T2:ERG score was higher in patients who had a Gleason score of 7 or greater, involvement of more than 50% of positive cores by cancer, and three or more positive cores.

“The T2:ERG assay significantly improved the diagnostic accuracy of a logistic regression model” for prostate cancer detection, said Dr. Amberson.

Dr. Wei and Dr. Amberson reported receiving research funding from Gen-Probe Inc. Some coauthors of both studies disclosed employment or leadership roles and stock ownership in Gen-Probe.

SAN FRANCISCO — A new urinary assay for a common gene rearrangement in prostate cancer improves the detection of this disease and the differentiation of its more aggressive forms, according to two cohort studies reported at a symposium on genitourinary cancers.

The studies, conducted among men who were scheduled for prostate biopsy or prostatectomy, found that the assay supplemented conventional risk factors for accurately identifying those having prostate cancer. In addition, higher assay scores correlated with the presence of adverse tumor features.

Dr. John T. Wei presented results of the first study on behalf of Sheila M.J. Aubin, Ph.D., of Gen-Probe Inc., the company that is developing the assay.

Prostate-specific antigen (PSA) level and digital rectal examination both have poor specificity for detecting prostate cancer. Moreover, these tests are unable to differentiate indolent from aggressive cancer, said the professor of urology at the University of Michigan in Ann Arbor.

About half of prostate cancers exhibit fusion of the androgen-regulated TMPRSS2 gene and the ERG oncogene. Cancers that harbor this fusion gene (abbreviated T2:ERG) have increased cell growth, invasion, and metastasis, and decreased apoptosis, Dr. Wei said at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

In the first study, the investigators assessed the performance of the novel assay, which measures levels of T2:ERG messenger RNA in urine, using urine specimens collected after digital rectal examination and before either prostate biopsy (623 men) or prostatectomy (142 men).

Analyses of biopsy-based indicators showed that the T2:ERG score was correlated with the number of cores that were positive, the percentage of cores that were positive, and the greatest percentage involvement of any core by cancer, according to Dr. Wei. Also, the median score was higher among patients with biopsy-significant cancer as defined by Epstein criteria.

Analyses of prostatectomy-based indicators showed that the T2:ERG score was correlated with the maximum tumor dimension. In addition, the median score was higher among patients who had an upgrade of the Gleason score between biopsy and prostatectomy, a prostatectomy Gleason score of greater than 6, and prostatectomy-significant cancer as defined from tumor characteristics.

Compared with the PCPT (Prostate Cancer Prevention Trial) risk score alone, the combination of this score with the T2:ERG score more accurately identified men who had prostate cancer (area under the curve, 0.75 vs. 0.65).

Dr. Wei noted that at cutoff scores of 100 and 200, the T2:ERG assay had high specificity for distinguishing between patients with and without cancer (88%–93%), with biopsy-significant and -insignificant cancer (85%–95%), and with prostatectomy-significant and -insignificant cancer (95%–100%).

Independent trials of the assay are needed, Dr. Wei acknowledged.

In the second study, investigators tested the same T2:ERG assay using urine specimens that were collected after digital rectal examination from 471 men who were scheduled for prostate cancer biopsy at community clinics, according to Dr. James B. Amberson.

Some 44% of patients had positive biopsies, he reported. The median age was 66 years in the patients with cancer and 63 years in the patients without it. The median serum PSA level was 5.0 and 4.3 ng/mL, respectively.

When used alone, the T2:ERG score had a high specificity (87%) for detection of biopsy-proven cancer, reported Dr. Amberson, divisional medical director of Dianon Systems Inc., the manufacturer of another test that was also used in the study. Sensitivity was 39%.

The median T2:ERG score was higher in patients who had a Gleason score of 7 or greater, involvement of more than 50% of positive cores by cancer, and three or more positive cores.

“The T2:ERG assay significantly improved the diagnostic accuracy of a logistic regression model” for prostate cancer detection, said Dr. Amberson.

Dr. Wei and Dr. Amberson reported receiving research funding from Gen-Probe Inc. Some coauthors of both studies disclosed employment or leadership roles and stock ownership in Gen-Probe.

SAN FRANCISCO — A new urinary assay for a common gene rearrangement in prostate cancer improves the detection of this disease and the differentiation of its more aggressive forms, according to two cohort studies reported at a symposium on genitourinary cancers.

The studies, conducted among men who were scheduled for prostate biopsy or prostatectomy, found that the assay supplemented conventional risk factors for accurately identifying those having prostate cancer. In addition, higher assay scores correlated with the presence of adverse tumor features.

Dr. John T. Wei presented results of the first study on behalf of Sheila M.J. Aubin, Ph.D., of Gen-Probe Inc., the company that is developing the assay.

Prostate-specific antigen (PSA) level and digital rectal examination both have poor specificity for detecting prostate cancer. Moreover, these tests are unable to differentiate indolent from aggressive cancer, said the professor of urology at the University of Michigan in Ann Arbor.

About half of prostate cancers exhibit fusion of the androgen-regulated TMPRSS2 gene and the ERG oncogene. Cancers that harbor this fusion gene (abbreviated T2:ERG) have increased cell growth, invasion, and metastasis, and decreased apoptosis, Dr. Wei said at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

In the first study, the investigators assessed the performance of the novel assay, which measures levels of T2:ERG messenger RNA in urine, using urine specimens collected after digital rectal examination and before either prostate biopsy (623 men) or prostatectomy (142 men).

Analyses of biopsy-based indicators showed that the T2:ERG score was correlated with the number of cores that were positive, the percentage of cores that were positive, and the greatest percentage involvement of any core by cancer, according to Dr. Wei. Also, the median score was higher among patients with biopsy-significant cancer as defined by Epstein criteria.

Analyses of prostatectomy-based indicators showed that the T2:ERG score was correlated with the maximum tumor dimension. In addition, the median score was higher among patients who had an upgrade of the Gleason score between biopsy and prostatectomy, a prostatectomy Gleason score of greater than 6, and prostatectomy-significant cancer as defined from tumor characteristics.

Compared with the PCPT (Prostate Cancer Prevention Trial) risk score alone, the combination of this score with the T2:ERG score more accurately identified men who had prostate cancer (area under the curve, 0.75 vs. 0.65).

Dr. Wei noted that at cutoff scores of 100 and 200, the T2:ERG assay had high specificity for distinguishing between patients with and without cancer (88%–93%), with biopsy-significant and -insignificant cancer (85%–95%), and with prostatectomy-significant and -insignificant cancer (95%–100%).

Independent trials of the assay are needed, Dr. Wei acknowledged.

In the second study, investigators tested the same T2:ERG assay using urine specimens that were collected after digital rectal examination from 471 men who were scheduled for prostate cancer biopsy at community clinics, according to Dr. James B. Amberson.

Some 44% of patients had positive biopsies, he reported. The median age was 66 years in the patients with cancer and 63 years in the patients without it. The median serum PSA level was 5.0 and 4.3 ng/mL, respectively.

When used alone, the T2:ERG score had a high specificity (87%) for detection of biopsy-proven cancer, reported Dr. Amberson, divisional medical director of Dianon Systems Inc., the manufacturer of another test that was also used in the study. Sensitivity was 39%.

The median T2:ERG score was higher in patients who had a Gleason score of 7 or greater, involvement of more than 50% of positive cores by cancer, and three or more positive cores.

“The T2:ERG assay significantly improved the diagnostic accuracy of a logistic regression model” for prostate cancer detection, said Dr. Amberson.

Dr. Wei and Dr. Amberson reported receiving research funding from Gen-Probe Inc. Some coauthors of both studies disclosed employment or leadership roles and stock ownership in Gen-Probe.