Du Shawn, Rossi Carmine, Khilfeh Ibrahim, Boonmak Porpong, Wong Gordon, Pilon Dominic, Ellis Lorie
Johnson & Johnson, Horsham, Pennsylvania.
Analysis Group, Inc., Montréal, Québec, Canada.
J Health Econ Outcomes Res. 2025 Jul 29;12(2):41-49. doi: 10.36469/001c.141170. eCollection 2025.
Prostate-specific antigen (PSA) has been used as both a screening tool and a marker for treatment response for advanced prostate cancer. With the introduction of androgen receptor pathway inhibitor (ARPI)-based treatment for metastatic castration-sensitive prostate cancer (mCSPC), there is a need to understand the impact that early treatment response, as measured by PSA, has on long-term clinical outcomes. To assess whether long-term indicators of treatment success differ among ARPI-naïve patients with mCSPC who did or did not attain ≥90% reduction in PSA levels within 6 months of treatment initiation. Patients with mCSPC initiating a first ARPI (ie, apalutamide, enzalutamide, abiraterone acetate, darolutamide) were identified using electronic medical record data linked to insurance claims in the United States (1/1/2016-9/30/2022). Eligible patients were classified based on whether they achieved ≥90% reduction in PSA measured between pre-treatment and a window of 30 to 180 days after ARPI initiation. Cohorts were balanced using inverse probability of treatment weighting. Weighted Kaplan-Meier analysis was used to compare overall survival and castration-resistance-free survival by 36 months post-index between those with and without ≥90% PSA reduction. Weighted cohorts included 1192 patients with early PSA reduction ≥90% and 699 without. By 36 months, significantly better overall survival was observed in those with early PSA reduction ≥90% than in those without (71.5% vs 54.7%; hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.31, 0.50; <.001). Similarly, significantly better castration-resistance-free survival was observed in those with early PSA reduction ≥90% than in those without (53.3% vs 36.8%; HR: 0.51, 95% CI: 0.43, 0.60; < .001). Early reduction of PSA levels by ≥90% within 6 months of ARPI initiation among patients with mCSPC in the real world is a robust indicator of treatment success, with improved long-term clinical outcomes, including survival and reduction in disease progression. These findings corroborate those of clinical trials and highlight the long-term benefits of an early and deep PSA response to ARPIs among real-world patients with mCSPC in the United States.
前列腺特异性抗原（PSA）一直被用作晚期前列腺癌的筛查工具和治疗反应标志物。随着基于雄激素受体通路抑制剂（ARPI）的转移性去势敏感性前列腺癌（mCSPC）治疗方法的引入，有必要了解以PSA衡量的早期治疗反应对长期临床结果的影响。为了评估在治疗开始后6个月内PSA水平降低≥90%的初治mCSPC患者与未达到该标准的患者之间，治疗成功的长期指标是否存在差异。利用与美国保险理赔相关联的电子病历数据，识别出开始使用第一种ARPI（即阿帕鲁胺、恩杂鲁胺、醋酸阿比特龙、达罗他胺）治疗的mCSPC患者（2016年1月1日至2022年9月30日）。符合条件的患者根据其在预处理和ARPI开始后30至１８０天窗口期内测量的PSA是否降低≥90%进行分类。采用治疗权重的逆概率对队列进行平衡。使用加权Kaplan-Meier分析比较PSA降低≥90%和未降低≥90%的患者在索引后36个月的总生存期和无去势抵抗生存期。加权队列包括1192例早期PSA降低≥90%的患者和699例未降低≥90%的患者。到36个月时，早期PSA降低≥90%的患者的总生存期明显优于未降低的患者（71.5%对54.7%；风险比[HR]：0.40，95%置信区间[CI]：0.31，0.50；P<0.001）。同样，早期PSA降低≥90%的患者的无去势抵抗生存期明显优于未降低的患者（53.3%对36.8%；HR：0.51，95%CI：0.43，0.60；P<0.001）。在现实世界中，mCSPC患者在ARPI开始后6个月内PSA水平早期降低≥90%是治疗成功的有力指标，长期临床结果得到改善，包括生存期延长和疾病进展减少。这些发现证实了临床试验的结果，并突出了美国现实世界中mCSPC患者对ARPI早期和深度PSA反应的长期益处。
