Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial
Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial
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DOI：
10.1016/s1470-2045(14)70040-3
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发表时间：
2014-04-01
期刊：
影响因子：
51.1
通讯作者：
Sydes, Matthew R.
中科院分区：
文献类型：
--
作者：
Dearnaley, David P.;Jovic, Gordana;Sydes, Matthew R.
背景：本试验的目的是比较局部前列腺癌患者的剂量递增适形放射治疗和对照剂量适形放射治疗。5年后报告的初步结果显示，递增剂量适形放射治疗改善了无生化进展的生存率。根据样本量计算，我们计划分析发生190例死亡时的总生存率；经过中位10年的随访，这一目标现在已经达到。方法RT01是一项3期开放的国际随机对照试验，纳入组织学确诊的T1b-T3a、N0、M0前列腺癌患者，前列腺特异性抗原低于50 ng/mL。患者按1：1的比例随机分配，使用基于计算机的最小化算法，根据精囊侵犯的风险分层，并集中到对照组(剂量，32次，试验设计时的标准剂量)或递增剂量组(74次，37次)。患者和调查人员都没有被分配到任务中。所有患者在开始适形放疗前接受新辅助雄激素剥夺治疗3~6个月，一直持续到适形放疗结束。主要预后指标为生化进展无进展生存期和总生存期。所有的分析都是在意向治疗的基础上进行的。治疗相关的副作用以前也有过报道。这项试验注册编号为ISRCTN47772397。在1998年1月7日至2001年12月20日期间，862名男性被注册，843人随后随机分配：422人被分到递增剂量组，421人被分配给对照组。截至2011年8月2日，已发生236例死亡：每组118例。中位随访率为10。0年(IQR 9.1-10.8)。每组10年的总生存率为71%(95%可信区间66-75)(风险比[HR]0.99，95%可信区间0)。77-1。28；p=0。96)。391名患者发生生化进展或进展性疾病(对照组221例[57%]，递增剂量组170例[43%])。10年后，对照组的无生化进展存活率为43%(95%可信区间38-48)，递增剂量组为55%(50-61)。在中位10年的随访期中，递增剂量适形放疗联合新辅助雄激素剥夺治疗在生化无进展生存率方面显示出优势，但这一优势并未转化为总体生存率的改善。这些递增剂量治疗的有效性数据必须与递增剂量相关的急性和晚期毒性增加进行权衡，并强调使用适当的现代放射治疗方法以减少副作用的重要性。
Background The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer. Preliminary findings reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival. Based on the sample size calculation, we planned to analyse overall survival when 190 deaths occurred; this target has now been reached, after a median 10 years of follow-up.Methods RT01 was a phase 3, open-label, international, randomised controlled trial enrolling men with histologically confi rmed T1b-T3a, N0, M0 prostate cancer with prostate specifi c antigen of less than 50 ng/ mL. Patients were randomly assigned centrally in a 1: 1 ratio, using a computer-based minimisation algorithm stratifying by risk of seminal vesicle invasion and centre to either the control group (64 Gy in 32 fractions, the standard dose at the time the trial was designed) or the escalated-dose group (74 Gy in 37 fractions). Neither patients nor investigators were masked to assignment. All patients received neoadjuvant androgen deprivation therapy for 3-6 months before the start of conformal radiotherapy, which continued until the end of conformal radiotherapy. The coprimary outcome measures were biochemical progression-free survival and overall survival. All analyses were done on an intention-to-treat basis. Treatment-related side-eff ects have been reported previously. This trial is registered, number ISRCTN47772397.Findings Between Jan 7, 1998, and Dec 20, 2001, 862 men were registered and 843 subsequently randomly assigned: 422 to the escalated-dose group and 421 to the control group. As of Aug 2, 2011, 236 deaths had occurred: 118 in each group. Median follow-up was 10 . 0 years (IQR 9 . 1-10.8). Overall survival at 10 years was 71% (95% CI 66-75) in each group (hazard ratio [HR] 0.99, 95% CI 0 . 77-1 . 28; p= 0 . 96). Biochemical progression or progressive disease occurred in 391 patients (221 [57%] in the control group and 170 [43%] in the escalated-dose group). At 10 years, biochemical progression-free survival was 43% (95% CI 38-48) in the control group and 55% (50-61) in the escalated-dose group (HR 0 . 69, 95% CI 0.56-0.84; p=0.0003).Interpretation At a median follow-up of 10 years, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These effi cacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-eff ects.