National Cancer Center Hospital East, Chiba, Japan.
BC Cancer Agency, Vancouver, BC, Canada.
Eur Urol. 2020 Apr;77(4):494-500. doi: 10.1016/j.eururo.2019.11.021. Epub 2019 Dec 13.
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).
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.
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).
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.
Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.
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.
LATITUDE 是一项随机、双盲试验，比较了醋酸阿比特龙联合泼尼松（AAP）+雄激素剥夺疗法（ADT）与安慰剂（PBO）+ADT 在高危转移性去势敏感前列腺癌（mCSPC）中的疗效。
评估前列腺特异性抗原（PSA）动力学与总生存期（OS）和影像学无进展生存期（rPFS）的相关性。
设计、地点和参与者：对 597 名接受 AAP+ADT 和 602 名接受 PBO+ADT 治疗的高危转移性去势敏感前列腺癌患者的数据进行了一项事后分析。
评估了与 PSA 相关的结局（根据前列腺癌工作组 2 标准，从基线 PSA 确认的 50%[PSA50]和 90%[PSA90]下降率、PSA<0.2ng/ml 的比例、中位 PSA 最低值、PSA 最低值时间[TPN]和 PSA 进展时间[TPP]与长期结局[OS 和 rPFS]的相关性）。使用 Cox 比例风险模型估计风险比（HR）。使用 Kendall's tau（KT）评估 TPP 与主要终点 rPFS 和 OS 的相关性。
与 PBO+ADT 相比，AAP+ADT 显著延迟了中位 TPP（33.2 与 7.4 个月；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%的患者出现 PSA50 应答，79%的患者出现 PSA90 应答（RR：1.36 和 2.30，均 p<0.001）。与无应答者相比，PSA50 和 PSA90 应答者的死亡风险降低（RR：0.44 和 0.12）。在 6 个月时，40%接受 AAP+ADT 治疗和 6.5%接受 PBO+ADT 治疗的患者 PSA 达到≤0.1ng/ml，与更长的 rPFS 和 OS 显著相关。AAP+ADT 的中位 PSA 最低值为 0.09ng/ml，而 PBO+ADT 为 2.36ng/ml。AAP+ADT 的中位 TPN（6.4 个月）与 rPFS 和 OS 呈正相关，而 PBO+ADT 的中位 TPN（3.8 个月）则相反。
与 ADT+PBO 相比，AAP+ADT 具有更好的 PSA 反应动力学，与高危 mCSPC 的 rPFS 和 OS 的长期结局具有强烈相关性。
我们发现，6 个月时 PSA 水平较低（≤0.1ng/ml）可能表明对治疗有良好的长期反应。我们的结果需要进一步证实。
