Biochemical recurrence after definitive prostate cancer therapy. Part I: Defining and localizing biochemical recurrence of prostate cancer*

Abstract

The introduction of prostate-specific antigen into clinical practice heralded a dramatic shift in the epidemiology of prostate cancer. The diagnosis and treatment of lower stage disease in younger men with fewer competing co-morbidities has resulted in a longer period of post-treatment cancer surveillance and the potential for disease recurrence. Life-long periodic prostate-specific antigen testing for biochemical recurrence is standard of care; however, there is no single definition of biochemical recurrence that reliably predicts clinical recurrence. This review explores the complexities of biochemical recurrence, a thorough understanding of which is crucial to making appropriate treatment decisions after primary treatment. It also evaluates the array of diagnostic tests frequently employed when biochemical recurrence has occurred. There is a disconnection between biochemical recurrence and progression to clinical disease. The definition of biochemical recurrence varies both by the prostate-specific antigen cut-point used and by the primary therapy employed. Furthermore, biochemical recurrence by itself appears not to be as reliable a predictor of eventual clinical recurrence as prostate-specific antigen doubling time. Current imaging modalities are rarely useful in localizing disease when biochemical recurrence is first detected. The correct interpretation of biochemical recurrence is crucial to treatment decision-making. New data show that prostate-specific antigen doubling time during prostate-specific antigen recurrence may be a valid surrogate for death from the disease. The potential therefore exists for prostate-specific antigen doubling time to be accepted as a trial endpoint, which might accelerate drug approval by the United States Food and Drug Administration.