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Rising PSA in Nonmetastatic Prostate Cancer

JUDD W. MOUL, MD
Division of Urologic Surgery and Duke Prostate Center
Duke University Medical Center

LIONEL L. BAÑEZ, MD
Division of Urologic Surgery and Duke Prostate Center
Duke University Medical Center

Urology Section, Durham Veterans Affairs Medical Center

STEPHEN J. FREEDLAND, MD
Division of Urologic Surgery and Duke Prostate Center
and Department of Pathology
Duke University Medical Center
Urology Section, Durham Veterans Affairs Medical Center
Durham, North Carolina

FINANCIAL DISCLOSURE: Dr. Moul is a speaker for AstraZeneca and sanofi-aventis. Dr. Bañez is a principal investigator in a sponsored grant for AstraZeneca. Dr. Freedland is a member of the advisory board and speakers bureau for AstraZeneca. Supported by the Department of Surgery, Duke University School of Medicine, Department of Veterans Affairs, the Department of Defense, and the American Urological Association Foundation/Astellas Rising Star in Urology Award.

ABSTRACT: 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.