Detection and Prognosis of Prostate Cancer

Although prostate specific antigen (PSA) has provided a useful marker for the detection and prognosis of prostate cancer, it is far from ideal, with a significant percent of false positive and false negative results for predicting a positive biopsy. Therefore, it is important to identify new markers that can enhance our ability to detect prostate cancer and predict the outcome of the disease. The Prostate Cancer Program has devoted considerable energies and expertise to identify new techniques and novel biomarkers for the detection and prognosis of prostate cancer.

Donald Tindall, Ph.D., and Karla Ballman, Ph.D., demonstrated that the dual-5_ reducatase inhibitor, dutasteride, inhibits fatty acid synthase (FASN) activity in prostate cancer cells. This is the first study to examine the effects of clinically relevant levels of dutasteride on prostate cancer cells at the molecular level and specifically demonstrate the inhibition of FASN in these cells.

George Klee, M.D., Ph.D., and Brian Davis, M.D., Ph.D., utilized LC-MS/MS quantification to identify Zn-alpha2 glycoprotein as a potential serum biomarker for prostate cancer. Their studies suggest that this LC-MS/MS assay is reproducible and can be used to evaluate the clinical utility of ZAG as a cancer biomarker.

Dr. Klee, along with George Vasmatzis, Ph.D., and John Cheville, M.D., optimized laser capture microdissection and RNA amplification for gene expression profiling of prostate cancer. Unsupervised clustering of the data was utilized to group and separate normal from benign prostatic hyperplasia cases and different Gleason patterns, as well as metastatic prostatic adenocarcinomas. Differential expression of alpha-methylacyl coenzyme A racemase (AMACR) and hepsin was confirmed using quantitative PCR.

Bradley Leibovich, M.D.; Eric Bergstralh, M.S.; Robert Myers, M.D.; and Michael Blute, M.D.; measured prostate specific antigen between 60 and 120 days following radical prostatectomy to assess its natural history and prognostic significance. They found that a detectable prostate specific antigen immediately following radical retropubic prostatectomy confers an increased risk of progression and death, but only in a subset of patients, who may be identified on the basis of pathological features and prostate specific antigen doubling time. In the future, such high risk patients may be suitable for trials of systemic therapy.

Drs. Blute, Leibovich, Myers, Cheville, along with Bergstralh and Thomas Sebo, M.D., studied trends in the distribution and prognostic significance of Gleason grades on radical retropubic prostatectomy specimens between 1989 and 2001. They confirmed that there were changes in the prevalence of Gleason grades on RRP specimens between 1989 and 2001. A chronological change in pathologic grading classification is suggested by evolving prognostic implications, which must be accounted for when comparing outcomes from different eras.

Drs. Blute, Myers, Leibovich, and statistician Bergstralh studied levels of increasing prostate specific antigen (PSA) following radical prostatectomy and adjuvant hormonal therapy. Their study demonstrated that many patients have slow progression despite increasing PSA following radical retropubic prostatectomy and adjuvant hormonal therapy. Nodal status, cancer grade and PSA doubling time are predictive of recurrence free survival and cancer specific survival, and may be a useful means of selecting patients for future adjuvant therapy trials.

They also studied the impact of patient age at time of treatment on the outcome following radical retropubic prostatectomy for prostate cancer. Their study found that, despite more favorable clinicopathological features, younger patients undergoing radical retropubic prostatectomy for prostate cancer have prostate cancer survival rates similar to that of older counterparts. They concluded that given the greater proportionate impact of prostate cancer on survival, it is particularly important to pursue aggressive treatment in younger patients.