Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany; Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada.
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Eur Urol Focus. 2022 Mar;8(2):399-408. doi: 10.1016/j.euf.2021.04.003. Epub 2021 Apr 11.
Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes.
To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs).
First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification.
The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone.
In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint.
We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.
新型前瞻性随机对照观察研究显示，转移性激素敏感型前列腺癌（mHSPC）的联合治疗具有良好的总生存期（OS）获益。
通过正式的网络荟萃分析（NMAs），比较这些新发现并对其进行系统回顾，这些 NMAs 纳入了其他前瞻性随机对照试验（RCTs）的观察结果。
首先，我们采用 PRISMA 方法，重点关注阿比特龙、恩扎卢胺、阿帕他胺和多西他赛在 mHSPC 中对 OS 的影响。我们在一线 mHSPC 中检索 PubMed 和摘要中的前瞻性 RCTs。其次，我们重点关注达到中位 OS 且对阿比特龙和多西他赛进行肿瘤负荷分层的 OS 检测的成熟研究。
第一部分纳入 7 项研究（n=6639），第二部分纳入 5 项研究（n=4462）。在第一部分中，阿比特龙在高肿瘤负荷 mHSPC 中排名第一。相反，恩扎卢胺在低肿瘤负荷 mHSPC 中排名第一。在第二部分中，高肿瘤负荷 mHSPC 中阿比特龙治疗的中位 OS 为 50.1 个月，超过了多西他赛（45.9 个月）和单独 ADT（34.0 个月）的中位 OS。低肿瘤负荷 mHSPC 中多西他赛治疗的中位 OS 为 69.5 个月，而单独 ADT 为 67.7 个月。
在依赖传统风险比的常规 NMAs 中，发现了所检查的联合治疗方法相对疗效的差异；在高肿瘤负荷 mHSPC 中，阿比特龙优于其他选择。在依赖中位 OS 可用的试验的第二部分中，与多西他赛相比，阿比特龙在高肿瘤负荷 mHSPC 中的 OS 差异为 4 个月。传统的 NMAs 可能高估了治疗效果的重要性，而不是关注中位 OS 持续时间，这可能是一个更重要的临床终点。
我们回顾了用于治疗前列腺癌已扩散到前列腺以外部位（转移性前列腺癌，mPC）的激素治疗和化疗研究。我们发现，在高肿瘤负荷 mPC 中，激素药物阿比特龙和低肿瘤负荷 mPC 中恩扎卢胺的总体生存最佳。与化疗药物多西他赛相比，mPC 患者使用阿比特龙的中位总生存期延长了 4 个月。
