6 个月时早期前列腺特异性抗原反应可预测转移性激素敏感前列腺癌的治疗效果：TITAN 试验的探索性分析。
Early Prostate-Specific Antigen Response by 6 Months Is Predictive of Treatment Effect in Metastatic Hormone Sensitive Prostate Cancer: An Exploratory Analysis of the TITAN Trial.
机构信息
Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois.
Case Western Reserve University, Cleveland, Ohio.
出版信息
J Urol. 2024 Nov;212(5):672-681. doi: 10.1097/JU.0000000000004158. Epub 2024 Jul 26.
PURPOSE
Early PSA response has been found to be prognostic of outcomes in metastatic hormone sensitive prostate cancer. We performed a secondary analysis of the TITAN trial to determine if early PSA response was predictive of treatment efficacy in metastatic hormone sensitive prostate cancer patients.
MATERIALS AND METHODS
Early PSA response was defined as achieving a PSA level of ≤ 0.2 ng/mL by 6 months of random assignment. A Cox proportional hazard model was constructed in a landmark population with an interaction term between the treatment and early PSA response to determine differential treatment effect on overall survival (OS). We applied multivariable Cox proportional hazard regression model with time to early PSA response fitted with restricted cubic spline to determine the association of time to early PSA response with OS.
RESULTS
Approximately 24% (124/524) of patients in the androgen deprivation therapy (ADT) alone group and 61% (321/524) in the apalutamide group had PSA response ≤ 0.2 ng/mL by 6 months. Longer time to early PSA response was associated with significantly superior OS in the apalutamide group. There was a significant difference in treatment effect from apalutamide on OS ( = .03 for interaction) among 6-month PSA responders (HR: 0.66; 95% CI: 0.44-1.00) vs nonresponders (HR: 1.14; 95% CI: 0.89-1.46). This difference in treatment effect was not statistically significant at 3 months ( = .17 for interaction). Among 6-month PSA responders, 3-year confounder-adjusted OS was 84% (80%-88%) for the apalutamide group and 74% (66%-82%) for the ADT alone group. Among nonresponders, 3-year adjusted OS for the 2 treatment arms were 58% (52%-65%) and 56% (51%-60%), respectively.
CONCLUSIONS
Early PSA response by 6 months was a predictor of treatment efficacy from ADT plus apalutamide on OS. Longer time to early PSA response was associated with superior OS in the apalutamide arm.
目的
早期 PSA 反应已被发现对转移性激素敏感前列腺癌的结局具有预后意义。我们对 TITAN 试验进行了二次分析，以确定早期 PSA 反应是否可预测转移性激素敏感前列腺癌患者的治疗效果。
材料和方法
早期 PSA 反应定义为在随机分组后 6 个月内 PSA 水平达到≤0.2ng/ml。在一个以治疗和早期 PSA 反应的交互项为基础的里程碑式人群中构建了 Cox 比例风险模型，以确定总体生存（OS）方面的治疗效果差异。我们应用多变量 Cox 比例风险回归模型，对早期 PSA 反应时间进行拟合限制立方样条，以确定早期 PSA 反应时间与 OS 的关联。
结果
在单独接受雄激素剥夺治疗（ADT）的患者中，约 24%（124/524）和接受阿帕鲁胺治疗的患者中，有 61%（321/524）在 6 个月时 PSA 反应≤0.2ng/ml。早期 PSA 反应时间较长与阿帕鲁胺组显著的 OS 获益相关。在 6 个月 PSA 反应者中（ =.03 交互作用），阿帕鲁胺对 OS 的治疗效果存在显著差异（HR：0.66；95%CI：0.44-1.00），而非反应者（HR：1.14；95%CI：0.89-1.46）。在 3 个月时，这种治疗效果差异无统计学意义（ =.17 交互作用）。在 6 个月 PSA 反应者中，阿帕鲁胺组的 3 年混杂因素调整 OS 为 84%（80%-88%），单独 ADT 组为 74%（66%-82%）。在无反应者中，两种治疗方法的 3 年调整 OS 分别为 58%（52%-65%）和 56%（51%-60%）。
结论
6 个月时的早期 PSA 反应是 ADT 加阿帕鲁胺治疗 OS 疗效的预测指标。早期 PSA 反应时间较长与阿帕鲁胺组的 OS 获益相关。
Zotero 插件