ImportanceMetastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to castration-resistant disease, the terminal phase. This review provides a summary of the most recent evidence for current and emerging management strategies, including treatment intensification with combinations of therapies. It also provides recommendations on applying the evidence in clinical practice to encourage appropriate treatment to improve survival outcomes among patients with metastatic hormone-sensitive prostate cancer.ObservationsAndrogen-deprivation therapy is the backbone of treatment for metastatic hormone-sensitive prostate cancer; however, it is insufficient alone to provide sustained disease control and long-term survival. Addition of an androgen receptor pathway inhibitor and/or docetaxel significantly improves survival, as demonstrated by several international phase 3 randomized clinical trials. Triplet therapy composed of androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel has been shown to improve overall survival over androgen-deprivation therapy plus docetaxel. In the ARASENS trial (darolutamide), the hazard ratios (HRs) were 0.68 (95% CI, 0.57-0.80) in the overall population; 0.71 (95% CI, 0.59-0.85) and 0.61 (95% CI, 0.35-1.05) in patients with de novo and recurrent disease, respectively; 0.69 (95% CI, 0.57-0.82) and 0.72 (95% CI, 0.41-1.13) in patients with high-volume and low-volume disease, respectively; and 0.71 (95% CI, 0.58-0.86) and 0.62 (95% CI, 0.42-0.90) in patients with high-risk and low-risk disease, respectively. In the PEACE-1 trial (abiraterone acetate + prednisone), the HRs were 0.75 (95% CI, 0.59-0.95; all de novo) in the overall population and 0.72 (95% CI, 0.55-0.95) and immature in the high-volume and low-volume subgroups, respectively. In the ENZAMET trial (enzalutamide), the HRs were 0.82 (95% CI, 0.63-1.06) in the overall population; 0.73 (95% CI, 0.55-0.99) and 1.10 (95% CI, 0.65-1.86) in the de novo and recurrent subgroups, respectively; and 0.87 (95% CI, 0.66-1.17) and 0.61 (95% CI, 0.33-1.10) in the high-volume and low-volume subgroups. Combination regimens are generally well tolerated, with adverse effects dependent on the profiles of the component drugs.Conclusions and relevanceThe findings of this review show compelling evidence from phase 3 randomized clinical trials in favor of initiating triplet combination therapy for patients with metastatic hormone-sensitive prostate cancer for the best overall survival. Patients who are eligible for chemotherapy should be offered androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel, particularly patients with high-volume, high-risk, or de novo metastatic disease.

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转移性激素敏感前列腺癌和联合治疗结果


重要性转移性激素敏感性前列腺癌目前是一种无法治愈的疾病。尽管雄激素剥夺疗法的反应率很高，但大多数病例都会进展为去势抵抗性疾病，即终末期。本综述总结了当前和新兴管理策略的最新证据，包括联合治疗的强化治疗。它还提供了在临床实践中应用证据的建议，以鼓励采取适当的治疗，以改善转移性激素敏感型前列腺癌患者的生存结果。观察雄激素剥夺疗法是转移性激素敏感型前列腺癌治疗的支柱；然而，仅靠它不足以提供持续的疾病控制和长期生存。多项国际 3 期随机临床试验表明，添加雄激素受体途径抑制剂和/或多西紫杉醇可显着提高生存率。由雄激素剥夺疗法加雄激素受体途径抑制剂加多西他赛组成的三联疗法已被证明比雄激素剥夺疗法加多西他赛可提高总体生存率。在 ARASENS 试验（达洛鲁胺）中，总体人群的风险比 (HR) 为 0.68（95% CI，0.57-0.80）；在新发疾病和复发性疾病患者中分别为 0.71 (95% CI, 0.59-0.85) 和 0.61 (95% CI, 0.35-1.05)；高容量和低容量疾病患者的该值分别为 0.69 (95% CI, 0.57-0.82) 和 0.72 (95% CI, 0.41-1.13)；在高风险和低风险疾病患者中，该风险分别为 0.71 (95% CI, 0.58-0.86) 和 0.62 (95% CI, 0.42-0.90)。在 PEACE-1 试验（醋酸阿比特龙 + 泼尼松）中，HR 为 0.75（95% CI，0.59-0.5）。95;总体人群中的成熟度为 0.72（95% CI，0.55-0.95），高容量和低容量亚组中的成熟度分别为 0.72（95% CI，0.55-0.95）和不成熟。在 ENZAMET 试验（恩杂鲁胺）中，总体人群的 HR 为 0.82（95% CI，0.63-1.06）；新发亚组和复发亚组分别为 0.73 (95% CI, 0.55-0.99) 和 1.10 (95% CI, 0.65-1.86)；高容量亚组和低容量亚组分别为 0.87 (95% CI, 0.66-1.17) 和 0.61 (95% CI, 0.33-1.10)。联合治疗方案通常具有良好的耐受性，不良反应取决于成分药物的特性。结论和相关性本次综述的结果显示，来自 3 期随机临床试验的令人信服的证据支持对转移性激素敏感前列腺患者开始三联疗法癌症以获得最佳的总体生存率。适合化疗的患者应接受雄激素剥夺疗法加雄激素受体途径抑制剂加多西他赛，特别是患有大容量、高风险或新发转移性疾病的患者。