Natural History of Biochemical Recurrence after Radical Prostatectomy: Risk Assessment for Secondary Therapy{A figure is presented}

Purpose: A persistently elevated or rising serum level of prostate-specific antigen (PSA) after radical prostatectomy is indicative of recurrent prostate cancer. The natural history of PSA-defined biochemical recurrence (BCR) is highly variable. While a rising PSA level universally antedates metastatic progression and prostate cancer-specific mortality (PCSM), it is not a surrogate for these endpoints. Thus, the management of patients with BCR is controversial. Methods: A literature review was conducted to determine the incidence and natural history of BCR, prognostic factors for clinical progression (CP), and the available evidence supporting local or systemic salvage therapy for these patients. Results: BCR is best defined as two successive PSA levels ≥0.4 ng/ml, as this correlates most accurately with CP. PSA doubling time (PSA-DT) and prostatectomy Gleason score are the variables that best predict the development of distant metastasis and PCSM. Prognostic models based on these and other variables are useful for assessing the need for salvage therapy and the anticipated outcome following local salvage therapy. A treatment algorithm for managing patients with post-prostatectomy BCR was devised. Conclusions: Management of patients with BCR after prostatectomy continues to be a complex and challenging issue. Improved methods for risk stratification allow for identification of patients who require treatment. Furthermore, these methods aid in determination of the pattern of disease recurrence, thereby guiding treatment modality. Randomized trials are essential to determine the value of local or systemic salvage therapy strategies in this patient population.