Kelly W K, Scher H I
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
J Urol. 1993 Mar;149(3):607-9. doi: 10.1016/s0022-5347(17)36163-3.
Post-therapy changes in prostate specific antigen (PSA) have been proposed as a surrogate end point for response in clinical trials of patients with hormone refractory prostatic cancer. While the specific criteria for response are evolving, there are concerns that changes in serum levels of PSA may be the result of changes in PSA expression or secretion independent of effects on cell growth and proliferation. We report 3 representative cases receiving complete androgen blockade with either gonadotropin-releasing hormone or orchiectomy plus the antiandrogen flutamide, which demonstrated sustained declines in serum PSA levels after discontinuation of the antiandrogen. Similar results have been observed in 6 additional patients. Whether this represents an agonist effect of the antiandrogen is unknown. The results suggest that a trial of flutamide withdrawal is justified in an asymptomatic patient with an increasing PSA before treatment with more toxic therapies. It also shows the importance of documenting sequential elevations in the marker before enrolling a patient in a clinical trial, and that changes in PSA must be interpreted cautiously in clinical trials when an antiandrogen is discontinued.
前列腺特异性抗原（PSA）治疗后的变化已被提议作为激素难治性前列腺癌患者临床试验中反应的替代终点。虽然反应的具体标准在不断演变，但有人担心血清PSA水平的变化可能是PSA表达或分泌变化的结果，而与对细胞生长和增殖的影响无关。我们报告了3例接受促性腺激素释放激素或睾丸切除术加抗雄激素氟他胺进行完全雄激素阻断治疗的代表性病例，这些病例在停用抗雄激素后血清PSA水平持续下降。另外6例患者也观察到了类似结果。这是否代表抗雄激素的激动剂效应尚不清楚。结果表明，对于在使用毒性更大的疗法治疗前PSA升高且无症状的患者，进行氟他胺撤药试验是合理的。这也表明在将患者纳入临床试验之前记录标志物的连续升高的重要性，并且在临床试验中当停用抗雄激素时，必须谨慎解释PSA的变化。
