背景:转移性去势抵抗性前列腺癌仍然是一种具有挑战性的治疗条件。在可用的治疗选择中,雄激素受体信号抑制剂醋酸阿比特龙+泼尼松(AA)和恩扎鲁他胺(恩扎),是目前临床实践中使用最多的一线疗法。然而,在这种情况下,仍然缺乏有效的临床预后指标。在这项研究中,我们的目的是根据接受AA或Enza作为一线治疗的mCRPC患者在AA/Enza发病时出现转移性疾病的时间(先前的局部治疗[PLT]或从头治疗[DN]后)和疾病负担(低容量[LV]或高容量[HV])评估预后模型.
方法:1月1日开始AA或Enza作为mCRPC一线治疗的连续患者队列,2015年4月1日,从9个美国和欧洲参与中心的临床和电子注册表中确定了2019年。根据转移性疾病出现时间(PLT或DN)和疾病体积(LV或HV;根据E3805试验,HV定义为在AA/Enza发作时存在内脏转移和/或至少4个骨转移,其中至少1个在轴向/骨盆骨骼中)。终点是总生存期,定义为从AA或Enza开始的时间,分别,死于任何原因或在最后一次随访中审查,以先发生者为准。
结果:在确定的417名合格患者中,157(37.6%)患有LV/PLT,87(20.9%)LV/DN,64(15.3%)HV/PLT,和109(26.1%)HV/DN。LV队列显示中位总生存期(59.0个月;95%CI,51.0-66.9个月)与HV队列(27.5个月;95%CI,22.8-32.2个月;P=0.0001),无论转移的时间。在多变量分析中,与LV患者相比,HV队列被证实预后较差(HV/PLT,HR=1.87;p=0.029;HV/DN,HR=2.19;P=0.002)。
结论:我们的分析表明,对于开始AA或Enza作为转移性去势抵抗性前列腺癌一线治疗的患者,疾病体积可能是预后因素。等待前瞻性临床试验验证。
Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line.
A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first.
Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002).
Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.