Prostate SPORE Project 1

Utility of serum and tissue biomarkers for predicting response to androgen deprivation therapy in the population of men with rising PSA following definitive treatment

Principal Investigator: George G. Klee, M.D., Ph.D.

The majority of men with prostate cancer are now diagnosed with cancers with a low risk of cause-specific mortality.^1-2 Such men are most frequently treated with primary definitive therapy including radical prostatectomy, external beam radiotherapy, or interstitial brachytherapy and are followed by regular serum PSA evaluations thereafter. Over a 5 to 10 year period, 15-30% of these men will be observed to have a rising PSA.^{3, 4, 5}

Of this group, some men will have obvious local recurrence or have clinically detectable metastasis, but many will have no other evidence of recurrent prostate cancer other than a rising or detectable PSA. These PSA relapses are conservatively estimated to affect approximately 50,000 men each year, define a rapidly growing population of major clinical and public health significance. The PSA "doubling time" has been identified as a potential surrogate for cause-specific mortality, and is used by some clinicians to determine which of these men deserve adjuvant hormonal ablation, local radiation therapy, or simple observation.^6-7

Biomarkers that could predict which of these men would benefit from any additional therapy are clearly needed. Genomic studies on prostate cancer tissue provide a good basis not only for tissue markers but also to identify candidates for potential serum biomarkers. Thus in this project we propose a clinical epidemiology study to evaluate and validate comprehensive tissue biomarker panels and to use data from these arrays to develop serum biomarker panels. We will then test both serum and tissue biomarker panels in a clinical trial intended to improve the care of patients with prostate cancer, and ultimately reduce the suffering and early death associated with prostate cancer progression.

1. Cooperberg MR. Lubeck DP. Meng MV. Mehta SS. Carroll PR. The changing face of low-risk prostate face of low-risk prostate cancer: trends in clinical presentation and primary management. Journal of Clinical Oncology. 22(11):2141-9, 2004.
2. D'Amico AV. Moul J. Carroll PR. Sun L. Lubeck D. Chen MH. Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era. Journal of Clinical Oncology. 21(11):2163-72, 2003
3. Amling CL. Blute ML. Bergstralh EJ. Seay TM. Slezak J. Zincke H. Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J Urol. 164(1):101-5, 2000
4. Shipley WU. Thames HD. Sandler HM. Hanks GE. Zietman AL. Perez CA. Kuban DA. Hancock SL. Smith CD. Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. JAMA. 281(17):1598-604, 1999
5. Kupelian PA. Potters L. Khuntia D. Ciezki JP. Reddy CA. Reuther AM. Carlson TP. Klein EA. Radical prostatectomy, external beam radiotherapy [72 Gy, external beam radiotherapy] or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. International Journal of Radiation Oncology, Biology, Physics. 58(1):25-33, 2004
6. D'Amico AV. Cote K. Loffredo M. Renshaw AA. Schultz D. Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer. Journal of Clinical Oncology. 20(23):4567-73, 2002
7. D'Amico AV. Moul JW. Carroll PR. Sun L. Lubeck D. Chen MH. Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy. Journal of the National Cancer Institute. 95(18):1376-83, 2003