临床进展与影像学进展对转移性去势抵抗性前列腺癌临床结局的影响。
Impact of clinical versus radiographic progression on clinical outcomes in metastatic castration-resistant prostate cancer.
机构信息
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; Weill Cornell Medical College, New York, United States.
出版信息
ESMO Open. 2020 Nov;5(6):e000943. doi: 10.1136/esmoopen-2020-000943.
OBJECTIVES
Unequivocal clinical progression (UCP)-a worsening of clinical status with or without radiographic progression (RAD)-represents a distinct mode of disease progression in metastatic prostate cancer. We evaluated the prevalence, risk factors and the impact of UCP on survival outcomes.
METHODS
A post-hoc analysis of the COU-AA-302, a randomised phase 3 study of abiraterone plus prednisone (AAP) versus prednisone was performed. Baseline characteristics were summarised. Cox proportional-hazards model and Kaplan-Meier method were used for survival and time to event analyses, respectively. Iterative multiple imputation method was used for correlation between clinicoradiographic progression-free survival (crPFS) and overall survival (OS).
RESULTS
Of 736 patients with disease progression, 280 (38%) had UCP-only and 124 (17%) had UCP plus RAD. Prognostic index model high-risk group was associated with increased likelihood of UCP (p<0.0001). Median OS was 25.7 months in UCP-only and 33.0 months for RAD-only (HR 1.39; 95% CI 1.16 to 1.66; p=0.0003). UCP adversely impacted OS in both treatment groups. Lowest OS was seen in patients with prostate specific antigen (PSA)-non-response plus UCP-only progression (median OS 22.6 months (95% CI 20.7 to 24.4)). Including UCP events lowered estimates of treatment benefit-median crPFS was 13.3 months (95% CI 11.1 to 13.8) versus median rPFS of 16.5 months (95% CI 13.8 to 16.8) in AAP group. Finally, crPFS showed high correlation with OS (r=0.67; 95% CI 0.63 to 0.71).
CONCLUSIONS
UCP is a common and clinically relevant phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with AAP or prednisone. UCP is prognostic and associated with inferior OS and post-progression survival. A combination of PSA-non-response and UCP identifies patients with poorest survival. When included in PFS analysis, UCP diminishes estimates of treatment benefit. Continued study of UCP in mCRPC is warranted.
目的
明确的临床进展（UCP）——伴有或不伴有影像学进展（RAD）的临床状况恶化——代表转移性前列腺癌的一种独特的疾病进展模式。我们评估了 UCP 的发生率、危险因素以及对生存结局的影响。
方法
对 COU-AA-302 的一项事后分析，这是一项阿比特龙加泼尼松（AAP）与泼尼松对照的随机 3 期研究。总结了基线特征。使用 Cox 比例风险模型和 Kaplan-Meier 方法分别进行生存和时间事件分析。迭代多重插补法用于临床影像学无进展生存（crPFS）和总生存（OS）之间的相关性分析。
结果
在 736 名疾病进展的患者中，280 名（38%）仅出现 UCP，124 名（17%）出现 UCP 加 RAD。预后指数模型高危组与 UCP 发生的可能性增加相关（p<0.0001）。仅出现 UCP 的患者中位 OS 为 25.7 个月，仅出现 RAD 的患者中位 OS 为 33.0 个月（HR 1.39；95%CI 1.16 至 1.66；p=0.0003）。UCP 对两组患者的 OS 均有不利影响。在 PSA 无反应且仅出现 UCP 进展的患者中，OS 最低（中位 OS 22.6 个月（95%CI 20.7 至 24.4））。纳入 UCP 事件会降低治疗获益的估计值，中位 crPFS 为 13.3 个月（95%CI 11.1 至 13.8），而 AAP 组中位 rPFS 为 16.5 个月（95%CI 13.8 至 16.8）。最后，crPFS 与 OS 高度相关（r=0.67；95%CI 0.63 至 0.71）。
结论
UCP 是接受 AAP 或泼尼松治疗的转移性去势抵抗性前列腺癌（mCRPC）患者中常见且具有临床意义的现象。UCP 具有预后意义，与较差的 OS 和进展后生存相关。PSA 无反应和 UCP 的联合可识别出生存最差的患者。当纳入 PFS 分析时，UCP 会降低治疗获益的估计值。需要进一步研究 mCRPC 中的 UCP。
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