Abstract：
BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2.
METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL).
RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms.
CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.
METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL).
RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms.
CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.
摘要：
背景：患者局部，不利的中危和高危前列腺癌在根治性前列腺切除术(RP)后复发风险增加.作者先前报道了这项2期试验的第一部分，测试新辅助阿帕鲁胺，阿比特龙,泼尼松,加上亮丙瑞林（AAPL）或阿比特龙，泼尼松,和亮丙瑞林（APL）6个月，然后RP。结果在20.3％的患者（n=24/118）中显示出良好的病理反应（肿瘤<5mm）。在这里，作者报告了第2部分的结果。
方法：对于第2部分，患者以1：1的比例随机接受AAPL治疗12个月（组2A）或观察（组2B），通过新辅助治疗和病理肿瘤分类进行分层。主要终点是3年生化无进展生存期。次要终点包括安全性和睾酮恢复(>200ng/dL)。
结果：总体而言，在第1部分纳入的118例患者中，有82例（69％）被随机分配到第2部分。未随机接受辅助治疗的患者中有较高比例的前列腺切除术病理反应良好（非随机患者为32.3％，而随机患者为17.1％）。在意向治疗分析中，组2A的3年生化无进展生存率为81%，组2B的3年无进展生存率为72%(风险比，0.81；90%置信区间，0.43-1.49）。在随机分组的患者中，AAPL组有81%的睾酮恢复，而观察组有95%的睾酮恢复，两组患者的中位恢复时间均<12个月。
结论：在这项研究中，因为30%的患者拒绝辅助治疗，B部分检测武器之间的差异的能力不足。未来的围手术期研究应以生物标志物为导向，并包括研究者和患者参与的策略，以确保符合协议程序。
方法：对于第2部分，患者以1：1的比例随机接受AAPL治疗12个月（组2A）或观察（组2B），通过新辅助治疗和病理肿瘤分类进行分层。主要终点是3年生化无进展生存期。次要终点包括安全性和睾酮恢复(>200ng/dL)。
结果：总体而言，在第1部分纳入的118例患者中，有82例（69％）被随机分配到第2部分。未随机接受辅助治疗的患者中有较高比例的前列腺切除术病理反应良好（非随机患者为32.3％，而随机患者为17.1％）。在意向治疗分析中，组2A的3年生化无进展生存率为81%，组2B的3年无进展生存率为72%(风险比，0.81；90%置信区间，0.43-1.49）。在随机分组的患者中，AAPL组有81%的睾酮恢复，而观察组有95%的睾酮恢复，两组患者的中位恢复时间均<12个月。
结论：在这项研究中，因为30%的患者拒绝辅助治疗，B部分检测武器之间的差异的能力不足。未来的围手术期研究应以生物标志物为导向，并包括研究者和患者参与的策略，以确保符合协议程序。
