Devos Gaëtan, Devlies Wout, De Meerleer Gert, Baldewijns Marcella, Gevaert Thomas, Moris Lisa, Milonas Daimantas, Van Poppel Hendrik, Berghen Charlien, Everaerts Wouter, Claessens Frank, Joniau Steven
Department of Urology, University Hospitals Leuven, Leuven, Belgium.
Department of development and regeneration, KU Leuven, Leuven, Belgium.
Nat Rev Urol. 2021 Dec;18(12):739-762. doi: 10.1038/s41585-021-00514-9. Epub 2021 Sep 15.
Patients with high-risk prostate cancer treated with curative intent are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death compared with patients treated for low-risk or intermediate-risk disease. Thus, these patients often need multimodal therapy to achieve complete disease control. Over the past two decades, multiple studies on the use of neoadjuvant treatment have been performed using conventional androgen deprivation therapy, which comprises luteinizing hormone-releasing hormone agonists or antagonists and/or first-line anti-androgens. However, despite results from these studies demonstrating a reduction in positive surgical margins and tumour volume, no benefit has been observed in hard oncological end points, such as cancer-related death. The introduction of potent androgen receptor signalling inhibitors (ARSIs), such as abiraterone, apalutamide, enzalutamide and darolutamide, has led to a renewed interest in using neoadjuvant hormonal treatment in high-risk prostate cancer. The addition of ARSIs to androgen deprivation therapy has demonstrated substantial survival benefits in the metastatic castration-resistant, non-metastatic castration-resistant and metastatic hormone-sensitive settings. Intuitively, a similar survival effect can be expected when applying ARSIs as a neoadjuvant strategy in high-risk prostate cancer. Most studies on neoadjuvant ARSIs use a pathological end point as a surrogate for long-term oncological outcome. However, no consensus yet exists regarding the ideal definition of pathological response following neoadjuvant hormonal therapy and pathologists might encounter difficulties in determining pathological response in hormonally treated prostate specimens. The neoadjuvant setting also provides opportunities to gain insight into resistance mechanisms against neoadjuvant hormonal therapy and, consequently, to guide personalized therapy.
与接受低风险或中风险疾病治疗的患者相比，接受根治性治疗的高危前列腺癌患者发生生化复发、转移进展和癌症相关死亡的风险更高。因此，这些患者通常需要多模式治疗以实现疾病的完全控制。在过去二十年中，已经使用传统的雄激素剥夺疗法进行了多项关于新辅助治疗的研究，传统雄激素剥夺疗法包括促黄体生成素释放激素激动剂或拮抗剂和/或一线抗雄激素药物。然而，尽管这些研究结果表明手术切缘阳性率和肿瘤体积有所降低，但在癌症相关死亡等硬性肿瘤学终点方面未观察到益处。强效雄激素受体信号抑制剂（ARSIs）的引入，如阿比特龙、阿帕他胺、恩杂鲁胺和达罗他胺，引发了人们对在高危前列腺癌中使用新辅助激素治疗的新兴趣。在雄激素剥夺治疗中添加ARSIs已在转移性去势抵抗性、非转移性去势抵抗性和转移性激素敏感性环境中显示出显著的生存益处。直观地说，在高危前列腺癌中应用ARSIs作为新辅助策略时，预计会有类似的生存效果。大多数关于新辅助ARSIs的研究使用病理终点作为长期肿瘤学结果的替代指标。然而，关于新辅助激素治疗后病理反应的理想定义尚未达成共识，病理学家在确定激素治疗的前列腺标本中的病理反应时可能会遇到困难。新辅助治疗环境也为深入了解对新辅助激素治疗的耐药机制提供了机会，从而指导个性化治疗。
