BERKELEY, CA (UroToday.com) - Despite much of the controversy surrounding the current screening and treatment patterns for prostate cancer, the fact remains that prostate cancer is still the second leading cause of cancer death among men in the United States.[1] Recent data confirm that the health care costs of men with bone metastases are substantially greater than for men without bony disease.[2, 3] Consequently, any improvement in accurately identifying men who are at highest risk for developing bone metastases is an increasingly urgent area of clinical need. To this point, risk stratification has been performed primarily using Prostate specific antigen (PSA)-based metrics such as PSA doubling time (PSADT) and baseline PSA.[4, 5] However, PSA-based metrics have also been less than satisfactory; in fact, one large trial was discontinued as a result of too few events5 and, in another, fewer than half of the patients enrolled had events,4 suggesting that there is room for improvement in our ability to identify men who are at risk for bone metastasis.
Aside from clinical trial accrual issues, a compelling health economic argument exists for improving our ability to identify men at high risk for bone metastases. Denosumab has been shown to delay bone metastases in men with castrate resistant prostate cancer (CRPC)4 and reduce skeletal related events.[6] However, zoledronic acid has also been shown to reduce SREs as well as reduce pain in men with bone metastases.[7, 8] Currently, zoledronic acid costs roughly half of what denosumab does. Given the ongoing emphasis on controlling costs of care for all diseases, and the fact that more money is typically spent in the final stages of cancer care, it is incumbent upon clinicians to employ any tools that can improve our ability to identify which patient populations will benefit most from a particular therapy. Thus, our finding that alkaline phosphatase velocity (APV) predicts not only overall survival but also bone metastasis-free survival (BMFS) independent of PSADT may be a step toward that goal.[9] Data such as these may enable clinicians to be proactive in answering these questions and generating outcomes that can be used to refine our practice patterns to optimally treat patients most likely to benefit, while minimizing over treatment.
It is our hope that these data on the predictive utility of APV[9] will prompt further investigation into better risk stratification of men with CRPC and advanced prostate cancer so that we can optimize outcomes, not only in terms of survival, but also quality of life, in a cost-effective way. We certainly do not suggest that APV is a substitute for PSA-based risk-stratification, only that it appears to enhance those metrics in identifying the men at highest risk for events. Of course, these data must be validated in other racially-diverse patient populations and evaluated prospectively, but we believe this is an exciting finding in an area of clinical need.
References:
- Siegel, R., Ma, J., Zou, Z., and Jemal, A.: Cancer statistics, 2014. CA Cancer J Clin, 64: 9, 2014.
- Schulman, K. L. and Kohles, J.: Economic burden of metastatic bone disease in the U.S. Cancer, 109: 2334, 2007.
- Seal, B., Sullivan, S. D., Ramsey, S. D., Asche, C. V., Shermock, K., Sarma, S. et al.: Comparing Hospital-Based Resource Utilization and Costs for Prostate Cancer Patients With and Without Bone Metastases. Appl Health Econ Health Policy, 2014.
- Smith, M. R., Saad, F., Oudard, S., Shore, N., Fizazi, K., Sieber, P. et al.: Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol, 31: 3800, 2013.
- Smith, M. R., Kabbinavar, F., Saad, F., Hussain, A., Gittelman, M. C., Bilhartz, D. L. et al.: Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol, 23: 2918, 2005.
- Fizazi, K., Carducci, M., Smith, M., Damiao, R., Brown, J., Karsh, L. et al.: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet, 377: 813, 2011.
- Saad, F., Gleason, D. M., Murray, R., Tchekmedyian, S., Venner, P., Lacombe, L. et al.: Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst, 96: 879, 2004.
- Saad, F., Gleason, D. M., Murray, R., Tchekmedyian, S., Venner, P., Lacombe, L. et al.: A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst, 94: 1458, 2002.
- Metwalli, A. R., Rosner, I. L., Cullen, J., Chen, Y., Brand, T., Brassell, S. A. et al.: Elevated alkaline phosphatase velocity strongly predicts overall survival and the risk of bone metastases in castrate-resistant prostate cancer. Urol Oncol, 32: 761, 2014.
Written by:
Adam R. Metwalli, MD,a Inger Lerra Rosner, MD,b and Jennifer Cullen Meyer, PhD, MPHc as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
aUrologic Oncology Branch, National Cancer Institute
National Institutes of Health
10 Center Drive, Building 10, Bethesda, MD 20892 USA
bDepartment of Defense, Center for Prostate Disease Research
1530 E. Jefferson Street, Rockville, MD 20852 USA
cDirector of Epidemiologic Research
Department of Defense, Center for Prostate Disease Research
1530 E. Jefferson Street, Rockville, MD 20852 USA