Abstract：
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.
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.
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.
摘要：
背景：先前的证据支持以初级放疗作为中危和高危局限性前列腺癌的初始治疗的雄激素剥夺疗法（ADT）。然而,前列腺癌根治术后术后放疗中ADT的使用和最佳持续时间仍不确定.
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。
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。
