摘要

BACKGROUND:LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC).
OBJECTIVE:To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS).
DESIGN, SETTING, AND PARTICIPANTS:A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT).
RESULTS AND LIMITATIONS:AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p <  0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p <  0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS.
CONCLUSIONS:Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.
PATIENT SUMMARY:We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.

译文

背景: LATITUDE 是一项随机、双盲试验，比较了醋酸阿比特龙和泼尼松 (AAP) 雄激素剥夺疗法 (ADT) 与安慰剂 (PBO) ADT 治疗高危转移性去势敏感前列腺癌 (mCSPC)。
目的: 评估前列腺特异性抗原 (PSA) 动力学与总生存期 (OS) 和放射学无进展生存期 (rPFS) 的相关性。
设计、设置和参与者: 对 597 名接受 aap  adadt 的男性和 602 名接受 PBO  adadt 的男性数据的事后分析。
结果测量和统计分析: PSA 相关结果的关联 (50% [PSA50] 和 90% [PSA90] 的确认率从基线 PSA [前列腺癌工作组 2 标准] 下降, PSA 的比率 <0.2 纳克/毫升，PSA 中位数最低点，PSA 最低点 [TPN] 的时间，以及 PSA 进展的时间 [TPP]评估长期结果 [OS 和 rPFS])。使用 Cox 比例风险模型估计风险比 (HRs)。使用 Kendall's tau (KT) 评估 TPP 与互质终点 rPFS 和 OS 的相关性。
结果和局限性: aap adadadt 显著延迟了中位数 TPP 与 pboadadadt (33.2 vs 7.4 mo; HR: 0.3，p <0.001)。TPP 与 rPFS (KT = 0.921) 和 OS (KT = 0.666) 相关。在 AAP ADT 组中，91% 的人有 PSA50，79% 的人有 PSA90 反应 (相对风险 [RR]: 分别为 1.36 和 2.30; 与 PBO ADT 相比，两次比较的 p <-0.001)。与无反应者相比，PSA50 和 PSA90 反应者的死亡风险降低 (RR: 分别为 0.44 和 0.12)。在 6 个月时，40% 接受 AAP ADT，6.5% 接受 PBO ADT，达到 PSA ≤ 0.1 ng/ml，这与较长的 rPFS 和 OS 显著相关。AAP ADT 的平均最低 PSA 为 0.09 ng/ml，而 PBO ADT 为 2.36 ng/ml。中位 TPN (AAP ADT，6.4 mo; PBO ADT，3.8 mo) 与 rPFS 和 OS 呈正相关。
结论: aap   adadt 与 adt   pbo 的卓越 PSA 反应动态与高危 mCSPC 的 rPFS 和 OS 的长期结果密切相关。
患者总结: 我们发现 6 个月后前列腺特异性抗原水平低 (≤ 0.1 纳克/毫升) 可能表明对治疗有良好的长期反应。我们的结果需要确认。