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Abstract：
BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after 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 radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, 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 distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
RESULTS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
CONCLUSIONS: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.
BACKGROUND: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after 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 radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, 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 distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
RESULTS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
CONCLUSIONS: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.
BACKGROUND: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
摘要：
背景：先前的证据表明佐剂，短期雄激素剥夺治疗(ADT)可提高中危和高危局限性前列腺癌的无转移生存率。然而,前列腺癌根治术后放疗中ADT的价值尚不清楚.
方法：RADICALS-HD是一项国际随机对照试验，用于测试ADT联合术后放疗对前列腺癌的疗效。关键的资格标准是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）接受单纯放疗（无ADT）或6个月ADT（短程ADT）放疗，每月皮下注射促性腺激素释放激素类似物，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远处转移或任何原因死亡。使用标准生存分析方法，考虑随机分层因素。该试验具有80％的功效，双侧α为5％，可检测10年无转移生存率从80％绝对增加到86％（风险比[HR]0·67）。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：在2007年11月22日至2015年6月29日之间，在加拿大121个中心，除了接受术后放疗外，还随机分配了1480名患者（中位年龄66岁[IQR61-69]），接受无ADT（n=737）或短期ADT（n=743）。丹麦,爱尔兰,和英国。中位随访时间为9·0年(IQR7·1-10·1)，据报道，268名参与者发生无转移生存事件(无ADT组142例，短程ADT组126例；HR0·886[95%CI0·688-1·140]，p=0·35）。无ADT组的10年无转移生存率为79·2％（95％CI75·4-82·5），短程ADT组为80·4％（76·6-83·6）。无ADT组的737名参与者中的121名（17％）和短程ADT组的743名参与者中的100名（14％）报告了3级或更高的毒性（p=0·15），没有治疗相关的死亡。
结论：前列腺癌根治术后卧床放疗后，转移性疾病并不常见。与无ADT相比，在这种放疗中添加6个月的ADT并未改善无转移生存率。这些发现不支持在该患者人群中使用短期ADT和术后放疗。
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是一项国际随机对照试验，用于测试ADT联合术后放疗对前列腺癌的疗效。关键的资格标准是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）接受单纯放疗（无ADT）或6个月ADT（短程ADT）放疗，每月皮下注射促性腺激素释放激素类似物，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远处转移或任何原因死亡。使用标准生存分析方法，考虑随机分层因素。该试验具有80％的功效，双侧α为5％，可检测10年无转移生存率从80％绝对增加到86％（风险比[HR]0·67）。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：在2007年11月22日至2015年6月29日之间，在加拿大121个中心，除了接受术后放疗外，还随机分配了1480名患者（中位年龄66岁[IQR61-69]），接受无ADT（n=737）或短期ADT（n=743）。丹麦,爱尔兰,和英国。中位随访时间为9·0年(IQR7·1-10·1)，据报道，268名参与者发生无转移生存事件(无ADT组142例，短程ADT组126例；HR0·886[95%CI0·688-1·140]，p=0·35）。无ADT组的10年无转移生存率为79·2％（95％CI75·4-82·5），短程ADT组为80·4％（76·6-83·6）。无ADT组的737名参与者中的121名（17％）和短程ADT组的743名参与者中的100名（14％）报告了3级或更高的毒性（p=0·15），没有治疗相关的死亡。
结论：前列腺癌根治术后卧床放疗后，转移性疾病并不常见。与无ADT相比，在这种放疗中添加6个月的ADT并未改善无转移生存率。这些发现不支持在该患者人群中使用短期ADT和术后放疗。
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。
