Selection of Optimal Neoadjuvant Therapy Before Cytoreductive Nephrectomy and Its Biomarker in Renal Cell Carcinoma

Cytoreductive nephrectomy (CN) has been a pivotal consideration in the treatment of metastatic renal cell carcinoma, with its role evolving significantly in the era of immuno-oncology (IO) therapies. This review examined the current evidence from randomized controlled trials and retrospective studies regarding the efficacy of upfront and deferred CN, particularly in the context of IO combination therapies. We explored patient stratification according to tumor burden and risk categories, emphasizing personalized treatment strategies that maximize therapeutic outcomes. For high-risk patients, early administration of IO therapies with strong antitumor effects is critical, whereas low-risk patients may benefit from upfront CN when combined with systemic therapies. Additionally, we discuss site-specific responses to IO therapies and highlight the importance of molecular profiles in guiding treatment choices. The development of biomarkers to dynamically monitor treatment efficacy will be essential in refining the role of CN and optimizing patient selection. This review underscores the need for further research to define the therapeutic potential of CN in the IO era.