[Current Systemic Therapy of Metastatic Renal Cell Carcinoma]

Metastatic clear cell renal cell carcinoma (mRCC) has undergone a fundamental therapeutic transformation over the past two decades. Following a prolonged period during which treatment options were limited to immunomodulatory therapies with modest efficacy due to the marked chemoresistance of this malignancy, the introduction of vascular endothelial growth factor receptor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) led to a substantial improvement in clinical outcomes. Currently, targeted therapies and the newer immune checkpoint inhibitors (ICIs) represent the central pillars of systemic treatment for mRCC. These combination therapies have increased the 5-year overall survival rate to over 40% and are now considered the standard of care (CheckMate 214, CheckMate 9ER, CLEAR, KEYNOTE-426). Nevertheless, there remains a significant unmet therapeutic need, particularly in later-line treatment settings, making the development of novel therapeutic strategies and more precise patient stratification essential for further improving clinical outcomes.