Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Cancer Risk Factors and Lifestyle Epidemiology Unit-ISPRO, Florence, Italy.
J Transl Med. 2023 Feb 3;21(1):75. doi: 10.1186/s12967-022-03861-2.
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.
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疾病。在现有的治疗选择中，雄激素受体信号抑制剂醋酸阿比特龙加泼尼松（AA）和恩扎鲁胺（Enza）是目前临床实践中最常用的一线治疗药物。然而，在这种情况下，仍然缺乏预后的验证性临床指标。在这项研究中，我们旨在评估一种基于转移性疾病发生时间（局部治疗后[PLT]或首发[DN]）和疾病负担（低体积[LV]或高体积[HV]）的预后模型，用于评估接受 AA 或 Enza 作为一线治疗的 mCRPC 患者。
从 9 个美国和欧洲参与中心的临床和电子登记处确定了 2015 年 1 月 1 日至 2019 年 4 月 1 日期间开始接受 AA 或 Enza 作为一线治疗的 mCRPC 连续患者队列。根据转移性疾病发生时间（PLT 或 DN）和疾病体积（根据 E3805 试验，HV 定义为存在内脏转移和/或至少 4 处骨转移，其中至少 1 处位于轴向/骨盆骨骼），将患者分为 4 组在 AA/Enza 发病时。终点是总生存时间，定义为从 AA 或 Enza 开始分别到任何原因死亡的时间，或以最后一次随访时间为准，以先发生者为准。
在 417 名符合条件的患者中，157 名（37.6%）为 LV/PLT，87 名（20.9%）为 LV/DN，64 名（15.3%）为 HV/PLT，109 名（26.1%）为 HV/DN。LV 队列的中位总生存时间（59.0 个月；95%CI，51.0-66.9 个月）优于 HV 队列（27.5 个月；95%CI，22.8-32.2 个月；P=0.0001），与转移性疾病的发生时间无关。多变量分析证实，与 LV 相比，HV 队列的预后较差（HV/PLT，HR=1.87；p=0.029；HV/DN，HR=2.19；P=0.002）。
我们的分析表明，在开始接受 AA 或 Enza 作为一线治疗转移性去势抵抗性前列腺癌的患者中，疾病体积可能是一个预后因素，有待前瞻性临床试验验证。
