Lionel L. Bañez, MD

Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.

Biomedical research is in themidst of unprecedented transformationstemming from theoverall impact of molecular biologyon medical research, including theemerging high-throughput genomicsbasedtechnologies. These new paradigmsare leading to better definitionof the disease state as well as moreprecise and less toxic therapeutic strategies.But even as we begin to understandthe implications of gene-basedinformation on the genesis, pathophysiology,and progression of disease andon the development of novel therapeuticapproaches, the dawn of theera of proteomics is heralding evenmore radical changes.