The Evolving Landscape of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma

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.

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study)

“…However, the data supporting CN in the modern era of IO combination therapies only come from retrospective analyses. The available data appear to be consistent, suggesting a positive impact of CN on OS of patients with mRCC, while it is performed before or after the initiation of systemic therapy represented by IO+IO or IO+TKI combinations [ 21 , 28 , 29 ].…”

The Metastasis Pattern of Renal Cell Carcinoma Is Influenced by Histologic Subtype, Grade, and Sarcomatoid Differentiation

“…While the overall 5-year relative survival rate for patients with kidney and renal pelvic cancers is 77.6%, the 5-year relative survival rate for patients with metastases is only 17.4%; in contrast, patients with localized disease had a 5-year relative survival rate of 92.9% [21]. Considering that approximately 15% of patients have metastatic disease at the time of diagnosis, a deeper understanding of the pathophysiology of metastatic RCC is important for improved treatment [21][22][23][24][25].…”