ROLE OF PROSTATE-SPECIFIC ANTIGEN AS A PREDICTOR OF OUTCOME IN PROSTATE-CANCER

Prostate-specific antigen (PSA) has been shown over the past few years to be a useful and sensitive marker for prostate cancer. During Phase III studies of the nonsteroidal antiandrogen, Casodex(R), in which di fferent doses were compared with castration (either surgical or medica l), serum PSA was measured on a regular basis. Attention was focused o n the change in serum PSA from baseline after 3 months Casodex treatme nt and also on the number of patients receiving Casodex whose PSA retu rned to the normal range. Data from trials comparing Casodex, 50 mg/da y, with castration showed a clear shortfall for Casodex compared with castration, in terms of percentage fall in PSA at 3 months, and also i n the number of patients whose PSA fell into the normal range after 3 months. Subsequent analysis showed, however, that the PSA level was re lated to outcome in terms of time to progression. These data allowed t he use of PSA to determine dose selection in a subsequent trial compar ing Casodex, 100 mg/day or 150 mg/day, with castration. At the time of dose selection, changes in PSA showed a statistically significant dif ference between Casodex, 100 mg/day, and castration, but no significan t difference between Casodex, 150 mg/day, and castration, either far t he change in PSA at 3 months or for the proportion of patients whose P SA had fallen into the normal range. The idea that serum PSA levels ca n predict outcome in prostate cancer and that they are correlated with other measures of outcome, such as time to progression, is supported by these data. A decrease in PSA is not a true surrogate endpoint in t hat it cannot predict the outcome for an individual patient with compl ete accuracy, but it does correlate well with other measures of outcom e, such as time to progression, for patient populations. (C) 1994 Wile y-Liss, Inc.