Prostate-Specific Antigen as a Marker of Disease Activity in Prostate Cancer : Part 2

Despite the impact of prostate-specific antigen (PSA) testing on the detection and management of prostate cancer, controversy about its usefulness as a marker of disease activity continues. This review, based on a recent roundtable discussion, examines whether PSA measurements can be used rationally in several clinical settings. Following radical prostatectomy and radiation therapy, prediction of survival by PSA level is most reliable in high-risk patients. PSA doubling time after radiation therapy is the strongest predictor of biochemical failure. PSA measurements have been associated with inconsistent results following hormonal treatment; reduced PSA levels may result from antiandrogen treatment, which decreases expression of the PSA gene, and therefore, the level of PSA production. In the setting of primary and secondary cancer prevention, PSA is important in risk stratification when selecting patients for studies. Part 2 of this two-part article, which began in the August issue, discusses the role of PSA in hormonal and drug therapies and in primary and secondary chemoprevention. [ONCOLOGY 16:1218-1236, 2002] In part 1 of this article, which was published in the August issue, we focused on the physiology of prostate-specific antigen (PSA), its measurement and use in clinical practice, and its predictive value following radical prostatectomy and radiation therapy. In part 2, we discuss the role of hormonal and drug therapies in the treatment of prostate cancer and how PSA defines the efficacy of these therapies. We also address the use of various chemopreventive agents such as diet, supplements, and drugs, and consider whether, in evaluating these approaches, an effect on PSA level means a corresponding effect on the disease process. PSA in Hormonal and Other Drug Therapies Hormonal therapy is the mainstay of treatment for prostate cancer that has recurred outside the prostate bed and the prostate following surgery or radiation therapy. A variety of medical and surgical options are available that affect points on the hypothalamic-pituitary-gonadal axis. Testicular androgen suppression is achieved with bilateral orchiectomy, estrogen therapy, androgen blockade with a luteinizing hormone-releasing hormone (LHRH) agonist such as goserelin (Zoladex) or leuprolide acetate (Lupron), or an LHRH receptor antagonist such as abarelix depot, which is under investigation in phase III studies.[1] Additional adrenal androgen suppression (resulting in total androgen ablation) is achieved by adding an oral antiandrogen to testicular ablation; bicalutamide (Casodex), flutamide (Eulexin), and nilutamide (Nilandron) have been approved by the US Food and Drug Administration. For most patients, these treatments are palliative. Following an initial response, progression (generally to an androgen-insensitive state) becomes manifest.