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. 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 , . 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. 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. Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

中文翻译：

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前列腺癌术后放疗雄激素剥夺疗法的持续时间：RADICALS-HD 随机试验中长程与短程雄激素剥夺疗法的比较


先前的证据支持雄激素剥夺疗法（ADT）和主要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 与术后放疗的使用和最佳持续时间仍不确定。 RADICALS-HD 是 RADICALS 方案中 ADT 持续时间的随机对照试验。在这里，我们报告了短程 ADT 与长程 ADT 的比较。关键资格标准是既往前列腺癌根治性切除术后的放疗指征、前列腺特异性抗原低于 5 ng/mL、不存在转移性疾病以及书面同意。参与者被随机分配 (1:1)，在放射治疗中添加 6 个月的 ADT（短程 ADT）或 24 个月的 ADT（长程 ADT），使用皮下注射促性腺激素释放激素类似物（短程 ADT 中每月一次）每日口服比卡鲁胺单药治疗 150 mg，或每月皮下注射地加瑞克。随机化是通过随机元素最小化集中完成的，在计算机系统中根据格里森评分、阳性切缘、放疗时间、计划放疗时间表和计划 ADT 类型进行分层。分配的治疗没有被掩盖。主要结局指标是无转移生存期，定义为前列腺癌引起的转移或任何原因导致的死亡。该比较的功效超过 80%，两侧 α 为 5%，可检测到 10 年无转移生存率从 75% 绝对增加到 81%（风险比 [HR] 0·72）。使用标准事件时间分析。分析遵循意向治疗原则。该试验已在 ISRCTN 注册中心注册，ISRCTN40814031 和 , 。 2008年1月30日至2015年7月7日期间，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）。除了加拿大、丹麦、爱尔兰和英国 138 个中心的术后放疗之外。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；HR 0·773 [95% CI 0·612–0·975]；p=0·029）。短程 ADT 组的 10 年无转移生存率为 71·9% (95% CI 67·6–75·7)，长程 ADT 组为 78·1% (74·2–81·5) ADT组。短程 ADT 组 753 名参与者中有 105 名 (14%) 和长程 ADT 组 757 名参与者中有 142 名 (19%) 报告了 3 级或以上毒性 (p=0·025)，没有发现与治疗相关的死亡。与增加 6 个月的 ADT 相比，增加 24 个月的 ADT 可以改善接受术后放疗的患者的无转移生存期。对于能够接受额外持续不良反应的个体，应在术后放疗的同时进行长程 ADT。英国癌症研究中心、英国研究与创新中心（前医学研究委员会）和加拿大癌症协会。