Sathianathen Niranjan J, Koschel Samantha, Thangasamy Isaac A, Teh Jiasian, Alghazo Omar, Butcher Georgiana, Howard Harriet, Kapoor Jada, Lawrentschuk Nathan, Siva Shankar, Azad Arun, Tran Ben, Bolton Damien, Murphy Declan G
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; Department of Surgery, Austin Health, The University of Melbourne, Parkville, Victoria, Australia.
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
Eur Urol. 2020 Mar;77(3):365-372. doi: 10.1016/j.eururo.2019.09.004. Epub 2019 Nov 1.
There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy.
To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC.
We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease.
We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37-0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons.
Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients.
Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.
在过去5年中，转移性激素敏感性前列腺癌（mHSPC）男性患者的治疗管理发生了重大变化，一线联合治疗已取代单纯雄激素剥夺治疗（ADT）。一系列治疗方法已进入该领域，但关于它们的相对疗效尚无明确答案。
进行系统评价和网状Meta分析，以明确mHSPC男性患者联合治疗方法的相对疗效。
我们检索了多个数据库以及截至2019年6月的主要会议摘要，以查找接受转移性疾病一线治疗的患者的随机试验，这些治疗包括ADT与一种（或多种）紫杉烷类化疗以及雄激素受体靶向治疗的联合应用。主要终点是总生存期（OS），我们将无进展生存期作为次要结局进行评估。我们根据疾病体积进行了亚组分析。
我们发现了7项符合我们纳入标准的试验，这些试验使用多西他赛、醋酸阿比特龙、恩杂鲁胺或阿帕他胺联合ADT。所有与ADT联合使用的药物均显示优于单纯ADT；与单纯ADT相比，恩杂鲁胺+ADT的绝对风险比最低（风险比0.53，95%置信区间0.37-0.75），与其他联合治疗或单纯ADT相比，其延长OS的首选治疗概率估计为76.9%。在疾病体积较小的男性中，恩杂鲁胺的OS似乎比多西他赛更好，但在其他比较中没有差异。
与单纯ADT相比，多西他赛、醋酸阿比特龙、恩杂鲁胺或阿帕他胺中的任何一种联合治疗均可显著延长OS。我们未发现不同联合治疗之间的OS存在显著差异。这些选择之间的细微差异为临床医生在为个体患者选择治疗方案时提供了相当大的灵活性。
许多转移性激素敏感性前列腺癌男性患者应采用一线联合治疗而非单纯雄激素剥夺治疗。临床医生在决策过程中可能会考虑许多因素，因此治疗应根据患者个体情况进行调整。
