Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France.
Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France; Bordeaux University, Bordeaux, France.
Cancer Treat Rev. 2021 Jun;97:102207. doi: 10.1016/j.ctrv.2021.102207. Epub 2021 Apr 12.
While many patients with non-metastatic renal cell carcinoma (RCC) can be cured with surgery alone, upward of 40% of patients recur in a short delay, raising the question of additional perioperative treatments. To address this clinical need, multiple trials have investigated the addition of systemic therapy after surgery in localized or locally advanced RCC. However, adjuvant systemic therapies in the past decades have provided disappointing results with only one positive study of antiangiogenic treatments. Debatable clinical benefit of adjuvant antiangiogenic tyrosine kinase inhibitors (TKIs) therapy at cost of high adverse event profiles have paved the way for development of alternative perioperative strategies, such as immune checkpoint inhibitors (ICIs). Further investigation into combination therapies with immunotherapy, neoadjuvant approaches and patient selection will be key to determining optimal adjuvant therapy regimens to improve outcomes and increase cure rates for patients with non-metastatic RCC. In this review, we extensively present the strong and weakness of the five adjuvant antiangiogenic TKI trials, highlight the main differences and discuss about the reasons of failure. We also expose the current ongoing clinical trials in the perioperative setting and provide new insights concerning the evolving landscape of the management of non-metastatic RCC.
虽然许多患有非转移性肾细胞癌 (RCC) 的患者仅通过手术即可治愈,但超过 40%的患者会在短时间内复发,这引发了对额外围手术期治疗的疑问。为了满足这一临床需求,多项临床试验已经研究了在局限性或局部进展性 RCC 中手术后添加系统治疗。然而,过去几十年中的辅助系统治疗仅提供了一项抗血管生成治疗的阳性研究结果,令人失望。辅助抗血管生成酪氨酸激酶抑制剂 (TKI) 治疗的临床获益存在争议,且具有较高的不良事件谱,这为开发替代围手术期策略(如免疫检查点抑制剂 (ICI))铺平了道路。进一步研究免疫治疗联合治疗、新辅助方法和患者选择将是确定最佳辅助治疗方案以改善非转移性 RCC 患者结局和提高治愈率的关键。在这篇综述中,我们广泛介绍了五项辅助抗血管生成 TKI 试验的优缺点,强调了主要差异,并讨论了失败的原因。我们还介绍了当前正在进行的围手术期临床试验,并就非转移性 RCC 管理的不断发展的格局提供了新的见解。