METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
RESULTS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
CONCLUSIONS: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
BACKGROUND: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
方法:RADICALS-HD是一项针对RADICALS方案中ADT持续时间的随机对照试验。这里,我们报告了短期和长期ADT的比较。关键的资格标准是既往前列腺癌根治术后的放疗指征,前列腺特异性抗原小于5ng/mL,没有转移性疾病,和书面同意。参与者被随机分配(1:1)在放疗中增加6个月的ADT(短期ADT)或24个月的ADT(长期ADT),使用皮下促性腺激素释放激素类似物(短期ADT组每月一次,长期ADT组每月一次),每日口服比卡鲁胺单药150毫克,或每月皮下degarelix。随机化是通过随机元素最小化来集中完成的,按格里森评分分层,正利润率,放疗时机,计划的放射治疗时间表,和计划的ADT类型,在计算机系统中。分配的治疗没有被掩盖。主要结果指标是无转移生存率,定义为前列腺癌引起的转移或任何原因死亡。比较具有超过80%的功效,双侧α为5%,可以检测到10年无转移生存率从75%绝对增加到81%(风险比[HR]0·72)。使用标准时间至事件分析。分析遵循意向治疗原则。该试验已在ISRCTN注册中心注册,ISRCTN40814031和ClinicalTrials.gov,NCT00541047.
结果:2008年1月30日至2015年7月7日,1523例患者(中位年龄65岁,IQR60-69)在加拿大138个中心被随机分配接受短期ADT(n=761)或长期ADT(n=762),以及术后放疗,丹麦,爱尔兰,和英国。中位随访时间为8·9年(7·0-10·0),总共报告了313例无转移生存事件(短程ADT组174例,长程ADT组139例;HR0·773[95%CI0·612-0·975];p=0·029)。短期ADT组的10年无转移生存率为71·9%(95%CI67·6-75·7),长期ADT组为78·1%(74·2-81·5)。短期ADT组753名参与者中的105名(14%)和长期ADT组757名参与者中的142名(19%)报告了3级或更高的毒性(p=0.025),没有治疗相关的死亡。
结论:与添加6个月的ADT相比,在接受术后放疗的患者中,增加24个月的ADT可改善无转移生存率.对于可以接受额外的不良反应持续时间的个人,术后放疗应提供长期ADT。
背景:英国癌症研究中心,英国研究与创新(原医学研究理事会),加拿大癌症协会。