Morote Juan, Orsola Anna, Planas Jacques, Trilla Enrique, Raventós Carles X, Cecchini Lluís, Catalán Roberto
Department of Urology, Vall d'Hebron Hospital and Autonoma University of Barcelona School of Medicine, Barcelona, Spain.
J Urol. 2007 Oct;178(4 Pt 1):1290-5. doi: 10.1016/j.juro.2007.05.129. Epub 2007 Aug 14.
We determined the testosterone castration level with clinical relevance in patients with prostate cancer on continuous androgen deprivation therapy. Secondary objectives were to analyze the role of associated bicalutamide in breakthrough increases of serum testosterone in these patients and the possible benefit of maximal androgen blockade.
Serum testosterone was determined 3 times (in 6 months) in 73 patients with nonmetastatic prostate cancer treated with medical castration, 28 (38.4%) of whom also received bicalutamide (maximal androgen blockade). During a mean followup of 51 months (range 12 to 240) 41 (67.1%) events of androgen independent progression were identified, and correlated with breakthrough testosterone increases of 50 ng/dl (classic level) and 20 ng/dl (surgical castration level).
Testosterone was less than 20 ng/dl in all determinations in 32 patients (43.6%). Breakthrough increases between 20 and 50 ng/dl were observed in 23 patients (31.5%), and increases greater than 50 ng/dl were observed in the remaining 18 (24.7%). The lowest testosterone level with a significant impact on survival free of androgen independent progression was 32 ng/dl. Mean survival free of androgen independent progression in patients with breakthrough increases greater than 32 ng/dl was 88 months (95% CI 55-121) while it was 137 months (95% CI 104-170) in those without breakthrough increases (p <0.03). Patients on maximal androgen blockade had an incidence of testosterone increase similar to those receiving monotherapy. However, maximal androgen blockade provided a significantly longer survival free of androgen independent progression in those with breakthrough increases greater than 50 ng/dl.
In the current report the lowest testosterone castration level with clinical relevance in medically castrated patients with prostate cancer was 32 ng/dl. Breakthrough increases greater than this threshold predicted a lower survival free of androgen independent progression. Maximal androgen blockade might benefit medically castrated cases of prostate cancer with breakthrough increases of more than 50 ng/dl.
我们确定了接受持续雄激素剥夺治疗的前列腺癌患者中具有临床相关性的睾酮去势水平。次要目标是分析联用比卡鲁胺在这些患者血清睾酮突破性升高中的作用以及最大雄激素阻断的潜在益处。
对73例接受药物去势治疗的非转移性前列腺癌患者的血清睾酮进行了3次测定（在6个月内），其中28例（38.4%）还接受了比卡鲁胺治疗（最大雄激素阻断）。在平均51个月（范围12至240个月）的随访期间，确定了41例（67.1%）雄激素非依赖性进展事件，并将其与睾酮突破性升高50 ng/dl（经典水平）和20 ng/dl（手术去势水平）相关联。
32例患者（43.6%）的所有测定中睾酮均低于20 ng/dl。23例患者（31.5%）观察到睾酮在20至50 ng/dl之间的突破性升高，其余18例（24.7%）观察到睾酮升高超过50 ng/dl。对无雄激素非依赖性进展生存期有显著影响的最低睾酮水平为32 ng/dl。睾酮突破性升高超过32 ng/dl的患者无雄激素非依赖性进展的平均生存期为88个月（95%可信区间55 - 121），而无突破性升高的患者为137个月（95%可信区间104 - 170）（p<0.03）。接受最大雄激素阻断治疗的患者睾酮升高的发生率与接受单一疗法的患者相似。然而，最大雄激素阻断为睾酮突破性升高超过50 ng/dl的患者提供了显著更长的无雄激素非依赖性进展生存期。
在本报告中，接受药物去势治疗的前列腺癌患者中具有临床相关性的最低睾酮去势水平为32 ng/dl。超过此阈值的突破性升高预示着无雄激素非依赖性进展生存期较短。最大雄激素阻断可能使睾酮突破性升高超过50 ng/dl的药物去势前列腺癌病例受益。
