The Evolving Landscape of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma

SIMPLE SUMMARY: For a significant period of time, the removal of the primary tumor termed cytoreductive nephrectomy has been considered the standard of care in patients with metastatic renal cell carcinoma. The situation is complicated because of a very quickly changing landscape of systemic therapy in metastatic renal cell carcinoma. After the turn of the century, cytokines were substituted by multiple tyrosine kinase inhibitors that dominated the therapy of renal carcinoma for more than a decade. With the expansion of immune-based systemic therapy, the importance of cytoreductive nephrectomy has been widely discussed and often disputed. Due to the absence of prospective data regarding the role of cytoreductive nephrectomy in the immunotherapy era, we can at this moment rely only on retrospective studies with relatively small numbers of patients. Nevertheless, with an individualized approach, we should attempt to identify in the clinical practice patients with favorable prognostic patterns who might benefit from the combination of surgery with systemic treatment. ABSTRACT: The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.