LAUSR

DOI:10.1097/MOU.0000000000000653 Over 65 000 new cases of kidney cancer are diagnosed in the United States annually, with nearly 15 000 attributable deaths each year. On the contrary, 30–40% of patients already harbor metastatic disease at presentation, and traditionally, 5-year survival rates for metastatic renal cell carcinoma (mRCC) have been dismal, ranging from only 0 to 20%. Fortunately, over the past decade – and even within the last year alone – the treatment paradigm for mRCC has shifted dramatically with the approval of several novel classes and combinations of systemic agents in this setting. Undoubtedly, the effective management of mRCC increasingly relies on a collaborative, multidisciplinary approach in which urologists, medical oncologists, and radiation oncologists play an integral role. Indeed, our armamentarium of therapeutic options for mRCC has evolved considerably since the original cytokine era of IFN-a and IL-2 that dominated throughout the 1980–1990s. Following this era, targeted therapies revolutionized outcomes in mRCC patients throughout the 2000s, with the introduction and approval of several new classes of drugs. This new approach was perhaps a first step toward precision medicine by targeting pathways involved in mRCC pathogenesis, including angiogenesis and mammalian target of rapamycin. Despite this, a large clinical gap remained for the handful of patients that were resistant to these targeted therapies. This unmet need ultimately led us into our third, contemporary therapeutic era of immune checkpoint inhibition, predicated by the CheckMate 025 and 214 trials. Ongoing efforts to predict therapeutic response and to develop novel therapies and combinatorial approaches for treating mRCC still continue to evolve at a rapid pace. With the emergence of these therapeutic classes, the role and timing of cytoreductive nephrectomy in the multimodal approach to managing mRCC has been a moving target. Potential advantages of cytoreductive nephrectomy include reducing the incidence of de-novo metastases, facilitating spontaneous regression, or palliating malignant symptoms or complications. However, these perceived benefits must be weighed against the risks of delayed initiation of systemic therapies, perioperative morbidity and mortality, and potentially adverse