Docetaxel Versus Surveillance After Radical Prostatectomy for High-risk Prostate Cancer: Results from the Prospective Randomised, Open-label Phase 3 Scandinavian Prostate Cancer Group 12 Trial
Docetaxel Versus Surveillance After Radical Prostatectomy for High-risk Prostate Cancer: Results from the Prospective Randomised, Open-label Phase 3 Scandinavian Prostate Cancer Group 12 Trial
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DOI：
10.1016/j.eururo.2018.01.012
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发表时间：
2018-06-01
期刊：
影响因子：
23.4
通讯作者：
Sengelov, Lisa
中科院分区：
文献类型：
--
作者：
Ahlgren, Goran M.;Flodgren, Per;Sengelov, Lisa
背景：辅助化疗是其他实体肿瘤的标准治疗方法，但迄今尚未被证明对前列腺癌有效。目的：评估高危前列腺癌根治性前列腺癌根治术后，单用6个周期的多西紫杉醇是否能提高无生化疾病生存率。设计、背景和参与者：开放标签、随机的多国3期试验。459例前列腺摘除术后患者入选。纳入标准：高危pt2切缘阳性或pT3a Gleason评分=4+3，pT3b或淋巴结阳性疾病Gleason评分=3+4。患者被分配(1：1)，每3周接受6个周期的多西紫杉醇75 mg/m(2)，不使用每日强的松(组A)或监测(组B)，直到达到终点。主要终点是前列腺特异性抗原进展=0.5 ng/ml。干预：前列腺切除术后多西紫杉醇治疗。干预：前列腺切除术后多西紫杉醇治疗。结果和限制：进展、死亡或最后一次随访的中位时间为56.8mo。在459名患者中有190名患者达到了主要终点--5年进展的风险为41%(A组45%，B组38%)。在Kaplan-Meier分析中有非比例风险的证据，所以我们使用限制性平均生存时间的差异作为效果的初步估计。限制到终点的平均生存时间，A组为43个月，B组为46个月(p=0.06)，差异无统计学意义，3.2个月(95%可信区间：6.7~-1.5个月)。A组和B组共记录了116例严重不良事件和41例严重不良反应，没有与治疗相关的死亡。并非所有患者都按方案接受了多西紫杉醇治疗。终点是生化进展，一些患者在终点之前接受了放射治疗。结论：多西紫杉醇在没有激素治疗的情况下并没有显著提高前列腺癌根治术后生化无病生存率。患者摘要：在这项随机试验中，我们测试了高危前列腺癌术后化疗是否降低了前列腺特异性抗原升高的风险。我们发现根治性前列腺切除术后给予多西紫杉醇没有任何益处。(C)2018年欧洲泌尿外科协会。爱思唯尔出版，版权所有。
Background: Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer.Objective: o evaluate whether six cycles of docetaxel alone improve biochemical disease-free survival after radical prostatectomy for high-risk prostate cancer.Design, setting, and participants: Open-label, randomised multinational phase 3 trial. Enrolment of 459 patients after prostatectomy. Inclusion criteria: high-risk pT2 margin positive or pT3a Gleason score >= 4+3, pT3b, or lymph node positive disease Gleason score >= 3 + 4. Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75 mg/m(2) every 3 wk without daily prednisone (Arm A) or surveillance (Arm B) until endpoint was reached. Primary endpoint was prostate-specific antigen progression >= 0.5 ng/ml. Intervention: Docetaxel treatment after prostatectomy.Intervention: Docetaxel treatment after prostatectomy.Results and limitations: Median time to progression, death, or last follow-up was 56.8 mo. Primary endpoint was reached in 190/459 patients-the risk of progression at 5 yr being 41% (45% in Arm A and 38% in Arm B). There was evidence of nonproportional hazards in Kaplan-Meier analysis, so we used the difference in restricted mean survival time as the primary estimate of effect. Restricted mean survival time to endpoint was 43 mo in Arm A versus 46 mo in Arm B (p = 0.06), a nonsignificant difference of 3.2 mo (95% confidence interval: 6.7 to - 1.5 mo). A total of 116 serious adverse events were recorded in Arm A and 41 in Arm B with no treatment-related deaths. Not all patients received docetaxel by protocol. The endpoint is biochemical progression and some patients received radiation treatment before the endpoint.Conclusions: Docetaxel without hormonal therapy did not significantly improve biochemical disease-free survival after radical prostatectomy.Patient summary: In this randomised trial, we tested whether chemotherapy after surgery for high-risk prostate cancer decreases the risk of a rising prostate-specific antigen. We found no benefit from docetaxel given after radical prostatectomy. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.