Department of Urology, Erasmus MC, Rotterdam, The Netherlands.
Eur Urol. 2009 Jan;55(1):14-22. doi: 10.1016/j.eururo.2008.09.008. Epub 2008 Sep 17.
The timing of endocrine treatment (ET) for prostate cancer (PCa) remains controversial. The issue is addressed in European Organisation for the Research and Treatment of Cancer (EORTC) protocol 30846 for patients with lymph node-positive (pN1-3) cancer without local treatment of the primary tumour.
To evaluate the effect of early versus delayed treatment in pN1-3 PCa.
DESIGN, SETTING, AND PARTICIPANTS: Two hundred thirty-four patients with histologically proven PCa and nodal metastases (pN1-3) were randomized to immediate versus delayed ET without treatment of the primary tumour. ET consisted of a depot luteinising hormone-releasing hormone (LHRH) agonist and 1 mo of an anti-androgen or surgical castration. The trial's main objective was to show non-inferiority of delayed ET to immediate ET by ruling out a hazard ratio (HR) of 1.50 for overall survival (OS), with 85% power at one-sided alpha=5%.
All but three patients were treated as randomized. The median follow-up is 13 yr. The median protocol treatment duration was 2.7 yr in the delayed and 3.2 yr in the immediate ET groups.
Overall, 193 patients (82.5%) have died (97 on delayed ET and 96 on immediate ET), 59.4% of them as a result of PCa. The intention-to-treat analysis shows a 22% increase in the hazard of death of those randomized to delayed treatment (HR=1.22, 95% confidence interval [CI]: 0.92, 1.62). The difference is not statistically significant, but non-inferiority is also not proved. The median OS on immediate ET is 7.6 yr (95% CI, 6.3-8.3 yr) versus 6.1 yr (95% CI, 5.7-7.3 yr) in the delayed ET group. The 10-yr cumulative incidence of death resulting from PCa was 55.6% in the delayed ET group versus 52.1% with immediate ET group. Similar conclusions hold for PCa-specific survival.
After 13 years of follow-up, survival or PCa-specific survival between immediate and delayed ET appear similar, but the trial is underpowered to reach its goal of showing non-inferiority.
前列腺癌（PCa）内分泌治疗（ET）的时机仍存在争议。欧洲癌症研究与治疗组织（EORTC）方案 30846 针对无局部肿瘤治疗的淋巴结阳性（pN1-3）癌症患者对此进行了探讨。
评估 pN1-3 PCa 中早期与延迟治疗的效果。
设计、设置和参与者：234 例组织学证实的 PCa 伴淋巴结转移（pN1-3）患者被随机分为即刻 ET 组与延迟 ET 组，两组均未对原发肿瘤进行治疗。ET 包括黄体生成素释放激素（LHRH）激动剂的 depot 制剂和 1 个月的抗雄激素或手术去势治疗。该试验的主要目的是通过排除总体生存（OS）风险比（HR）为 1.50 来证明延迟 ET 不劣于即刻 ET，单侧α=5%时具有 85%的效能。
除 3 例患者外，其余患者均按随机分组进行治疗。中位随访时间为 13 年。延迟 ET 组和即刻 ET 组的中位方案治疗持续时间分别为 2.7 年和 3.2 年。
共有 193 例（82.5%）患者死亡（延迟 ET 组 97 例，即刻 ET 组 96 例），其中 59.4%死于 PCa。意向治疗分析显示，随机接受延迟治疗的患者死亡风险增加了 22%（HR=1.22，95%置信区间[CI]：0.92，1.62）。差异无统计学意义，但也未证明非劣效性。即刻 ET 组的中位 OS 为 7.6 年（95%CI：6.3-8.3 年），而延迟 ET 组为 6.1 年（95%CI：5.7-7.3 年）。延迟 ET 组 10 年累积 PCa 死亡率为 55.6%，即刻 ET 组为 52.1%。PCa 特异性生存的结论相似。
随访 13 年后，即刻 ET 与延迟 ET 的生存或 PCa 特异性生存似乎相似，但该试验的效能不足以证明非劣效性。
