Barragan-Carrillo Regina, Saad Eddy, Saliby Renee-Maria, Sun Maxine, Albiges Laurence, Bex Axel, Heng Daniel, Mejean Arnaud, Motzer Robert J, Plimack Elizabeth R, Powles Thomas, Rini Brian I, Zhang Tian, Choueiri Toni K
Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Eur Urol. 2025 Feb;87(2):143-154. doi: 10.1016/j.eururo.2024.10.019. Epub 2024 Nov 6.
The treatment landscape for metastatic renal cell carcinoma (mRCC) has evolved significantly in recent years, leading to improved outcomes. The aim of this review is to provide clinicians with a practical guide for selecting first- and second-line treatments on the basis of current evidence.
We critically evaluated systemic treatment strategies for mRCC. A comprehensive literature search was conducted in PubMed and Embase, alongside manual searches of guidelines and conference proceedings up to October 2024. A narrative review was performed to reach a consensus, with voting used to resolve differing opinions among authors.
First-line treatment options include immune checkpoint inhibitor (ICI)-based combinations or tyrosine kinase inhibitors (TKIs). Four combination regimens have been approved internationally. Owing to the lack of head-to-head trials and standardized biomarkers, treatment decisions rely on factors such as International Metastatic RCC Database Consortium (IMDC) risk score, functional status, safety profiles, sarcomatoid features, use of immunosuppressive drugs, and need for immediate response. Despite advances, many patients will experience disease progression on ICI-based therapy, necessitating further treatment. The need for standardized second-line approaches remains unmet. TKIs, alone or with everolimus, show promising efficacy, while HIF2a inhibitors offer newer options with a favorable toxicity profile. Rechallenge with ICIs after early progression is not recommended.
For optimal mRCC treatment selection, clinicians must carefully balance efficacy, toxicity, and patient preferences, especially when transitioning between first- and second-line therapies, to provide individualized care.
近年来，转移性肾细胞癌（mRCC）的治疗格局发生了显著变化，治疗效果得到改善。本综述的目的是根据当前证据为临床医生提供选择一线和二线治疗的实用指南。
我们对mRCC的全身治疗策略进行了严格评估。在PubMed和Embase上进行了全面的文献检索，并手动检索了截至2024年10月的指南和会议记录。进行了叙述性综述以达成共识，通过投票解决作者之间的不同意见。
一线治疗选择包括基于免疫检查点抑制剂（ICI）的联合治疗或酪氨酸激酶抑制剂（TKI）。四种联合治疗方案已在国际上获得批准。由于缺乏头对头试验和标准化的生物标志物，治疗决策依赖于国际转移性肾细胞癌数据库联盟（IMDC）风险评分、功能状态、安全性、肉瘤样特征、免疫抑制药物的使用以及对即时反应的需求等因素。尽管取得了进展，但许多患者在基于ICI的治疗中仍会出现疾病进展，需要进一步治疗。对标准化二线治疗方法的需求仍未得到满足。TKI单独使用或与依维莫司联合使用显示出有前景的疗效，而HIF2a抑制剂提供了毒性特征良好的新选择。不建议在早期进展后重新使用ICI。
为了优化mRCC的治疗选择，临床医生必须仔细权衡疗效、毒性和患者偏好，尤其是在一线和二线治疗之间转换时，以提供个性化护理。
