Blackledge G R, Lowery K
Medical Research Department, Zeneca Pharmaceuticals, Macclesfield, UK.
Prostate Suppl. 1994;5:34-8. doi: 10.1002/pros.2990250710.
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, in which different doses were compared with castration (either surgical or medical), serum PSA was measured on a regular basis. Attention was focused on the change in serum PSA from baseline after 3 months Casodex treatment and also on the number of patients receiving Casodex whose PSA returned to the normal range. Data from trials comparing Casodex, 50 mg/day, with castration showed a clear shortfall for Casodex compared with castration, in terms of percentage fall in PSA at 3 months, and also in the number of patients whose PSA fell into the normal range after 3 months. Subsequent analysis showed, however, that the PSA level was related to outcome in terms of time to progression. These data allowed the use of PSA to determine dose selection in a subsequent trial comparing Casodex, 100 mg/day or 150 mg/day, with castration. At the time of dose selection, changes in PSA showed a statistically significant difference between Casodex, 100 mg/day, and castration, but no significant difference between Casodex, 150 mg/day, and castration, either for the change in PSA at 3 months or for the proportion of patients whose PSA had fallen into the normal range. The idea that serum PSA levels can 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 that it cannot predict the outcome for an individual patient with complete accuracy, but it does correlate well with other measures of outcome, such as time to progression, for patient populations.
在过去几年中，前列腺特异性抗原（PSA）已被证明是前列腺癌的一种有用且敏感的标志物。在非甾体类抗雄激素药物康士得（Casodex）的III期研究中，将不同剂量的康士得与去势（手术去势或药物去势）进行比较，并定期测量血清PSA。研究重点关注康士得治疗3个月后血清PSA相对于基线的变化，以及接受康士得治疗且PSA恢复到正常范围的患者数量。比较每天50毫克康士得与去势治疗的试验数据显示，与去势相比，康士得在3个月时PSA下降的百分比以及3个月后PSA降至正常范围的患者数量方面明显不足。然而，后续分析表明，PSA水平在疾病进展时间方面与预后相关。这些数据使得在随后一项比较每天100毫克或150毫克康士得与去势治疗的试验中能够利用PSA来确定剂量选择。在选择剂量时，PSA的变化显示每天100毫克康士得与去势之间存在统计学显著差异，但每天150毫克康士得与去势之间，无论是3个月时PSA的变化还是PSA降至正常范围的患者比例，均无显著差异。这些数据支持了血清PSA水平可预测前列腺癌预后且与其他预后指标（如疾病进展时间）相关的观点。PSA的降低并非真正的替代终点，因为它不能完全准确地预测个体患者的预后，但对于患者群体而言，它确实与其他预后指标（如疾病进展时间）有很好的相关性。
