Prostate-Specific Antigen as a Marker of Disease Activity in Prostate Cancer : Part 1 Review

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 1 of this two-part article, which concludes in the September issue, focuses on the physiology of PSA, its measurement and use in clinical practice, and its predictive value following radical prostatectomy and radiation therapy. [ONCOLOGY 16:1024-1051, 2002] Prostate-specific antigen (PSA) testing has changed early detection and management of prostate cancer dramatically since its introduction into clinical practice in the early 1980s. Nevertheless, its usefulness as a marker of disease activity and its correlation with survival remain controversial because, in some disease settings, definitive data are lacking for its rational use. This review defines the clinical settings in which PSA can be rationally used as an indicator of disease activity and therapeutic effectiveness. Because the natural history of prostate cancer can be long—20 to 50 years in some cases—it is impractical to use survival as the only test of a therapy’s usefulness in clinical trials. This is especially true of chemopreventive agents that are active at the earliest stages of a disease that may not be detectable for as long as 20 years. Even the longest-running trial of a potential chemopreventive therapy—the Selenium and Vitamin E Cancer Prevention Trial (SELECT)—is slated for only 12 years.[1] Using a marker of disease activity as an end point to demonstrate therapeutic efficacy is imperative for trials at various stages of the disease process. Because patients are encouraged to participate in early-detection programs for some cancers at age 40, the time from early detection to clinical diagnosis of recurrent disease may be as long as 10 years, and the time from diagnosis to death may be another 20 to 30 years after definitive therapy—timelines that would pose practical impossibilities for clinical trials. FIGURE 1 Algorithm for Estimating the Likelihood of Remaining Free of Metastatic Disease After Initial PSA Recurrence