Prostate-Specific Membrane Antigen Expression Predicts Prostate Cancer Recurrence

Cytogen Corporation recently announced the presentation of clinical data demonstrating that a high level of prostate-specific membrane antigen (PSMA) in prostate tissue is a strong predictor of prostate cancer recurrence. The data were presented at the 101st American Urological Association (AUA) Annual Meeting held May 20-25 in Atlanta.

In the study, independent investigators from Ulm, Germany, and Boston analyzed PSMA expression by tissue microarray in 96 patients with either localized or metastatic prostate cancer who had undergone radical prostatectomy, or surgical removal of the prostate, as monotherapy. One-third of the patients had disease confined to the prostate gland with no spread to lymph nodes, 33% had only one positive lymph node, and the remaining third had more than one positive lymph node. Following therapy, patients were monitored for a maximum of 12.6 years with an average follow-up of 2.7 years.

PSMA is a protein abundantly expressed on the surface of prostate cancer cells, with an increased expression in high-grade cancers, metastatic disease, and hormone-refractory prostate cancer. PSMA is also present at high levels on the neovasculature needed for the growth and survival of many solid tumors. In contrast to other prostate-related antigens such as prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and prostate secretory protein, PSMA is a membrane glycoprotein that is not secreted. These unique attributes make PSMA an excellent target for monoclonal antibody diagnostic and therapeutic options in prostate and potentially other cancers.

Study Results

Significant upregulation of PSMA expression was noted in patients with metastatic disease as compared to those with localized prostate cancer and in localized disease compared to benign prostate tissue (P < .05). High PSMA levels were associated with a significant increase in disease recurrence following therapy (P < .001) in univariate statistical analyses.

Other significant parameters for predicting disease recurrence included lymph node positivity, extraprostatic extension of disease, seminal vesicle invasion by disease, and Gleason score of 8 to 10. Using multivariate statistical analyses, the best model to predict disease recurrence included high PSMA expression (

P

< .01) and extraprostatic extension (

P

= .02) after adjusting for Gleason score and seminal vesicle invasion.

Independent Predictor

"We are very encouraged by the findings of this new study, which validate and extend upon data previously published demonstrating that overexpression of PSMA in primary prostate cancer not only correlates with other adverse traditional prognostic factors, but can independently predict both a higher incidence and shorter time to disease recurrence," said Michael D. Becker, president and chief executive officer of Cytogen. "There is a tremendous need for better prognostic markers in prostate cancer to assist in the identification of patients with aggressive forms of the disease who can potentially benefit from earlier and more intensive forms of treatment. The findings presented at AUA further support our belief in the importance of PSMA as an independent prostate cancer marker and important diagnostic and therapeutic target."