Novel biomarker may measure prostate cancer aggressiveness

SAN DIEGO – Prostate-specific antigen peptidase activity is higher in patients with less-aggressive prostate cancer than in patients with advanced disease, results from a pilot study demonstrated.

If the finding is confirmed by larger studies, this marker "may improve identification of men who may be better candidates for active surveillance," Dr. William J. Catalona said at the annual meeting of the American Urological Association. "In our study, if you considered those patients, it may have delayed or prevented surgery in 22% of this study population."

The marker, an assay developed by Ohmx under a National Institutes of Health small-business grant, "is a completely different approach to PSA testing," said Dr. Catalona, professor of urology at Northwestern University, Chicago.

"Current prostate cancer detection techniques generally suffer from a limited ability to differentiate indolent from aggressive prostate cancers," he explained. "We’re looking for tests that would detect life-threatening prostate cancer. That’s the real challenge in front of us today."

PSA peptidase activity was measured in a blinded study of 100 randomly selected patients who were treated with radical retropubic prostatectomy. Of the 100 patients, 50 had aggressive disease (defined as cancer resulting in prostate cancer–specific death, lymph node or distant metastases, seminal vesicle invasion, or extracapsular tumor extension), and 50 had nonaggressive disease (defined as cancer with a Gleason score of 6 or lower, pathologic stage T2, and no evidence of clinical or biochemical tumor recurrence on follow-up of 2-5 years). At surgery, fluid from the excised gland was gently milked from the apical urethral stump into a 2-mL conical vial and was immediately frozen at –80° C.

Next, researchers used a fluorogenic peptide probe to measure the level of proteolytic enzyme activity of PSA (aPSA) in each sample.

"All PSA tests measure the amount of PSA," said Dr. Catalona, who developed the PSA as a screening test for prostate cancer. "What this test focuses on is the enzymatic activity of PSA in prostatic fluid."

The aPSA value was significantly higher in patients with nonaggressive disease, compared with their counterparts who had advanced disease (a mean of 865 mcg/mL vs. a mean of 518 mcg/mL), a difference Dr. Catalona described as "striking." This reciprocal relationship between the PSA peptidase activity among the two patient groups "may improve identification of men who may be better candidates for active surveillance."

On receiver operating characteristic analysis, aPSA and the normalized ratio of aPSA to serum total PSA had the highest discriminatory power for predicting the presence of aggressive prostate cancer. Dr. Catalona estimated that using aPSA as an aggressiveness biomarker could result in 22% of the patients diagnosed with nonaggressive prostate cancer being able to avoid or delay radical prostatectomy.

Dr. Catalona said he and his associates plan to expand studies of the biomarker to include samples collected retrospectively before surgery, during attentive digital rectal exam.

The study was supported in part by a grant from the National Institutes of Health. Dr. Catalona disclosed that he received grant and research support from Beckman Coulter, Ohmx, and deCODE Genetics.

dbrunk@frontlinemedcom.com

SAN DIEGO – Prostate-specific antigen peptidase activity is higher in patients with less-aggressive prostate cancer than in patients with advanced disease, results from a pilot study demonstrated.

If the finding is confirmed by larger studies, this marker "may improve identification of men who may be better candidates for active surveillance," Dr. William J. Catalona said at the annual meeting of the American Urological Association. "In our study, if you considered those patients, it may have delayed or prevented surgery in 22% of this study population."

The marker, an assay developed by Ohmx under a National Institutes of Health small-business grant, "is a completely different approach to PSA testing," said Dr. Catalona, professor of urology at Northwestern University, Chicago.

"Current prostate cancer detection techniques generally suffer from a limited ability to differentiate indolent from aggressive prostate cancers," he explained. "We’re looking for tests that would detect life-threatening prostate cancer. That’s the real challenge in front of us today."

PSA peptidase activity was measured in a blinded study of 100 randomly selected patients who were treated with radical retropubic prostatectomy. Of the 100 patients, 50 had aggressive disease (defined as cancer resulting in prostate cancer–specific death, lymph node or distant metastases, seminal vesicle invasion, or extracapsular tumor extension), and 50 had nonaggressive disease (defined as cancer with a Gleason score of 6 or lower, pathologic stage T2, and no evidence of clinical or biochemical tumor recurrence on follow-up of 2-5 years). At surgery, fluid from the excised gland was gently milked from the apical urethral stump into a 2-mL conical vial and was immediately frozen at –80° C.

Next, researchers used a fluorogenic peptide probe to measure the level of proteolytic enzyme activity of PSA (aPSA) in each sample.

"All PSA tests measure the amount of PSA," said Dr. Catalona, who developed the PSA as a screening test for prostate cancer. "What this test focuses on is the enzymatic activity of PSA in prostatic fluid."

The aPSA value was significantly higher in patients with nonaggressive disease, compared with their counterparts who had advanced disease (a mean of 865 mcg/mL vs. a mean of 518 mcg/mL), a difference Dr. Catalona described as "striking." This reciprocal relationship between the PSA peptidase activity among the two patient groups "may improve identification of men who may be better candidates for active surveillance."

On receiver operating characteristic analysis, aPSA and the normalized ratio of aPSA to serum total PSA had the highest discriminatory power for predicting the presence of aggressive prostate cancer. Dr. Catalona estimated that using aPSA as an aggressiveness biomarker could result in 22% of the patients diagnosed with nonaggressive prostate cancer being able to avoid or delay radical prostatectomy.

Dr. Catalona said he and his associates plan to expand studies of the biomarker to include samples collected retrospectively before surgery, during attentive digital rectal exam.

The study was supported in part by a grant from the National Institutes of Health. Dr. Catalona disclosed that he received grant and research support from Beckman Coulter, Ohmx, and deCODE Genetics.

dbrunk@frontlinemedcom.com

SAN DIEGO – Prostate-specific antigen peptidase activity is higher in patients with less-aggressive prostate cancer than in patients with advanced disease, results from a pilot study demonstrated.

If the finding is confirmed by larger studies, this marker "may improve identification of men who may be better candidates for active surveillance," Dr. William J. Catalona said at the annual meeting of the American Urological Association. "In our study, if you considered those patients, it may have delayed or prevented surgery in 22% of this study population."

The marker, an assay developed by Ohmx under a National Institutes of Health small-business grant, "is a completely different approach to PSA testing," said Dr. Catalona, professor of urology at Northwestern University, Chicago.

"Current prostate cancer detection techniques generally suffer from a limited ability to differentiate indolent from aggressive prostate cancers," he explained. "We’re looking for tests that would detect life-threatening prostate cancer. That’s the real challenge in front of us today."

PSA peptidase activity was measured in a blinded study of 100 randomly selected patients who were treated with radical retropubic prostatectomy. Of the 100 patients, 50 had aggressive disease (defined as cancer resulting in prostate cancer–specific death, lymph node or distant metastases, seminal vesicle invasion, or extracapsular tumor extension), and 50 had nonaggressive disease (defined as cancer with a Gleason score of 6 or lower, pathologic stage T2, and no evidence of clinical or biochemical tumor recurrence on follow-up of 2-5 years). At surgery, fluid from the excised gland was gently milked from the apical urethral stump into a 2-mL conical vial and was immediately frozen at –80° C.

Next, researchers used a fluorogenic peptide probe to measure the level of proteolytic enzyme activity of PSA (aPSA) in each sample.

"All PSA tests measure the amount of PSA," said Dr. Catalona, who developed the PSA as a screening test for prostate cancer. "What this test focuses on is the enzymatic activity of PSA in prostatic fluid."

The aPSA value was significantly higher in patients with nonaggressive disease, compared with their counterparts who had advanced disease (a mean of 865 mcg/mL vs. a mean of 518 mcg/mL), a difference Dr. Catalona described as "striking." This reciprocal relationship between the PSA peptidase activity among the two patient groups "may improve identification of men who may be better candidates for active surveillance."

On receiver operating characteristic analysis, aPSA and the normalized ratio of aPSA to serum total PSA had the highest discriminatory power for predicting the presence of aggressive prostate cancer. Dr. Catalona estimated that using aPSA as an aggressiveness biomarker could result in 22% of the patients diagnosed with nonaggressive prostate cancer being able to avoid or delay radical prostatectomy.

Dr. Catalona said he and his associates plan to expand studies of the biomarker to include samples collected retrospectively before surgery, during attentive digital rectal exam.

The study was supported in part by a grant from the National Institutes of Health. Dr. Catalona disclosed that he received grant and research support from Beckman Coulter, Ohmx, and deCODE Genetics.

dbrunk@frontlinemedcom.com