How Much Can We Rely on the Level of Prostate-Specific Antigen as an End Point for Evaluation of Clinical Trials? A Word of Caution!

Abstract

of PSA levels. The study objectives were to determine whether serum PSA changes were associated with the survival duration and to define the role of PSA levels as a surrogate end point for response to suramin treatment. The results, similar to those reported by others (9), indicated that a decline in PSA levels was a weak, but statistically significant, predictor of survival duration. Further evaluation of the data collected within the context of a landmark analysis (10), however, failed to identify a threshold value that would permit use of PSA-level decline as a response indicator. Thus, serum PSA levels, at least at this time, may not be the optimum marker of treatment response in advanced hormone-refractory prostate cancer. It is interesting that the statistical analyses by Sridhara et al. (8) also revealed that a 75% or greater decline in PSA levels was not more predictive of survival duration than was a 50% decline in PSA levels. Although this result may imply that suramin responses may not affect survival duration, this could also be explained by a possible confounding biological effect of suramin on PSA expression, not necessarily indicative of antitumor activity, as was suggested by Thalmann et al. (5). Clearly, more clinical data are needed to further characterize the significance of PSA changes with regard to the therapeutic benefits of suramin on prostate cancer. To this end, suramin is being tested in a prospectively randomized, placebo-controlled, multi-institutional study sponsored by Parke-Davis, Ann Arbor, MI, in which quality of life, time to disease progression, survival duration, and serial changes in PSA levels are being evaluated simultaneously. The implications of the study by Thalmann et al. (5) may actually be even broader than asserted by the authors, since similar effects on PSA expression have been reported with other drugs, including agents commonly used to treat prostate cancer, such