Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
J Urol. 2023 Mar;209(3):532-539. doi: 10.1097/JU.0000000000003084. Epub 2023 Feb 9.
This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer.
PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and values were based on an unstratified Cox proportional analysis model.
In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively.
There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer.
本 PROSPER 事后分析评估了恩扎卢胺治疗去势抵抗性前列腺癌非转移性患者中 PSA 下降深度与临床结局之间的关系。
PROSPER 是一项国际性、随机、双盲、安慰剂对照的 III 期临床试验，结果表明与安慰剂相比，雄激素剥夺治疗加恩扎卢胺可显著改善无转移生存期和总生存期。本事后分析共纳入 905 例恩扎卢胺治疗的患者。无转移生存期（主要终点）和总生存期（次要终点）根据 PSA 下降的 4 个相互排斥的亚组进行评估：<50%（参照）；≥50%~<90%；≥90%，最低值≥0.2ng/mL；和≥90%，最低值<0.2ng/mL。采用 12 个月的时间节点分析确定中位数和 95%置信区间；风险比和 P 值基于无分层 Cox 比例分析模型。
在恩扎卢胺治疗的患者中，PSA 下降<50%、≥50%~<90%、≥90%且最低值≥0.2ng/mL、和≥90%且最低值<0.2ng/mL 分别与无转移生存期的中位时间（95%置信区间）为 22.1（14.8-未达到）、34.2（29.4-未达到）、36.6（33.4-未达到）和未达到有关，总生存期的中位时间（95%置信区间）为 40.8（31.7-44.9）、54.4（49.0-67.0）、64.3（63.4-未达到）和未达到，分别。
PSA 下降幅度与临床结局之间存在统计学显著相关性，表明在非转移性去势抵抗性前列腺癌中，PSA 水平变化与临床结局之间存在以前被低估的关系。
