本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(24)00549-X

摘要内容如下：

背景

先前的证据支持雄激素剥夺疗法（ADT）联合放疗作为中危和高危局限性前列腺癌的初始治疗。然而，根治性前列腺切除术后ADT的使用和术后放疗的最佳持续时间仍不确定。

方法

Radicals-HD是Radicals方案中ADT持续时间的随机对照试验。在此，我们报告了短程与长程ADT的比较。主要入选标准为既往前列腺癌根治性前列腺切除术后的放疗指征、前列腺特异性抗原低于5 ng/mL、无转移性疾病和书面同意。参与者被随机分配（1:1）在放疗的基础上增加6个月的ADT（短程ADT）或24个月的ADT（长程ADT），使用皮下促性腺激素释放激素类似物（短程ADT组每月一次，长程ADT组3个月一次），每日口服比卡鲁胺单药治疗150 mg，或每月皮下注射Degarelix。在计算机系统中，通过随机元素的最小化集中进行随机化，根据Gleason评分、阳性切缘、放疗时间、计划的放疗时间表和计划的ADT类型进行分层。分配的治疗未被屏蔽。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引起的死亡。在双侧α为5%的情况下，检测10年无转移生存率的绝对增加从75%增加到81%（风险比[HR]0.72）的比较具有超过80%的功效。使用标准的时间-事件分析。分析遵循意向治疗原则。该试验已在ISRCTN Registry（ISRCTN40814031）和ClinicalTrials.gov（NCT00541047）注册。

调查结果

在2008年1月30日至2015年7月7日期间，在加拿大、丹麦、爱尔兰和英国的138个中心，1523名患者（中位年龄65岁，IQR 60-69）被随机分配接受短程ADT（n=761）或长程ADT（n=762）以及术后放疗。中位随访时间为8.9年（7.0-10.0），共报告313例无转移生存事件（短期ADT组174例，长期ADT组139例；HR 0.773[95%CI 0.612-0.975]；P=0.029）。短程ADT组10年无转移生存率为71.9%（95%CI 67.6~75.7），长程ADT组为78.1%（95%CI 74.2~81.5）。短期ADT组753名参与者中有105名（14%）和长期ADT组757名参与者中有142名（19%）报告了3级或更高的毒性（P=0.025），无治疗相关死亡。

解释

与增加6个月的ADT相比，增加24个月的ADT提高了接受术后放疗的患者的无转移生存率。对于能够接受额外的不良反应持续时间的患者，应在术后放疗的同时提供长疗程的ADT。

英文原文如下：

Abstracts

BACKGROUND  Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.

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.

FINDINGS  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.

INTERPRETATION  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.

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。