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.
ESMO Open. 2020 Nov;5(6):e000943. doi: 10.1136/esmoopen-2020-000943.
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.
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).
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).
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.
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。
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。
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）。
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。
