Contemporary Management of Metastatic Renal Cell Carcinoma - Episode 4

Cytoreductive Nephrectomy in Metastatic RCC

Transcript: Daniel J. George, MD: Joe, we’ve got these intermediate- and sometimes poor-risk patients that present to you with their primary tumor in place. They’ve got metastases. In the era now of these newer IO [immuno-oncology] therapy regimens, how are you managing the role of cytoreductive nephrectomy? What are some of the more recent data out there regarding that? How is that translating into practice?

Chung-Han Lee, MD, PhD: I think it’s always been kind of a long-standing thing that there was this idea that everyone went to cytoreductive based off some retrospective series. But now as the data have matured more than retrospective studies, they really have highlighted the need for good patient selection. The big clinical trial that came out that probably started challenging people’s thoughts about whether or not everyone needs cytoreductive was the CARMENA trial—a randomized trial of either immediate sunitinib or up-front cytoreductive nephrectomy followed by sunitinib.

The idea was to show that up-front sunitinib was noninferior than the idea of cytoreductive. However, to the surprise of everyone, the study has really shown that harm is actually being done to very, very poor-risk patients. Certainly there’s been a lot of criticism about the trial. But that being said, for these very, very sick patients, many of whom during that period in which they’re getting cytoreductive, you know you never even needed to get sunitinib. Part of it is really talking about who is the patient in which we can wait versus the patients who need immediate treatment. I think that’s probably going to be very important in the TK [tyrosine kinase]-IO setting and also important in the IO/IO setting with ipilimumab-nivolumab.

Daniel J. George, MD: I think there’s going to continue to be a need for more data here as our treatments evolve. Nizar, you all have done a lot of work with systemic therapy before surgery, both in the neoadjuvant setting as well as even in the metastatic setting with metastasectomy. Walk us a little bit through the multidisciplinary University of Texas MD Anderson Cancer Center approach to this.

Nizar M. Tannir, MD, FACP: The management of a patient with metastatic RCC [renal cell carcinoma] and the role of cytoreductive nephrectomy that incorporated a surgical management into the overall management came from when we didn’t have really effective systemic therapy back in the cytokine era with interferon, and that continued. But obviously now we have more effective therapy, in my opinion.

The question is not whether to do or never to do cytoreductive nephrectomy; it is the timing. In my opinion, now every patient should be given the opportunity of having systemic therapy up front. After you give them 3 months or a little bit more or less of systemic therapy, then you decide, depending on the response, whether you do cytoreductive nephrectomy later on. It is possible that now with the immune checkpoint inhibitors—whether we’re doing nivolumab-ipilimumab or a TKI plus checkpoint inhibitors—we may delay the need for cytoreductive nephrectomy. Who knows, we may reach a situation when we don’t need to do cytoreductive nephrectomy on many of those patients.

The way we approach it at The University of Texas MD Anderson Cancer Center, to answer your question, Dan, is now we try to enroll patients on trials. In fact, we did conduct this randomized phase II trial of 104 patients that will be presented by my colleague Jianjun Gao, MD, in the oral session of renal, where we took patients who had metastatic disease and primary in place, and we randomized them to receive 2 cycles of nivolumab-ipilimumab, or nivolumab plus bevacizumab, or nivolumab alone. Then we did scans again after 6 weeks and those patients who had stable disease or responded and had a surgical resectable mass—whether it’s the kidney, primary, or a mass, metastatic site—we went ahead and did the cytoreductive nephrectomy later.

What that trial showed us is that there is a potential for us to achieve a pathological CR [complete response] in the primary and in the metastasis. It is unlike treating them in the era where we did sunitinib and bevacizumab, etc., with these patients with metastatic disease. Here the concern is not with wound healing, because you’re not giving them a VEGF [vascular endothelial growth factor], anti-VEGF agent.

I think this is the new paradigm: to treat with systemic therapy up front. Six weeks, 2 cycles may not be sufficient. I advocate for actually 4 cycles, 12 weeks and then response. And if you have a response, then to consider nephrectomy in that setting.

Daniel J. George, MD: That’s great. I mean, you’ve heard a lot of different approaches to this. I think you’re going to hear and see variations on this. But I think the idea is more and more treating with systemic therapy up front, not if we’re going to do but when we’re going to do nephrectomy and recognizing the opportunity maybe for clinical trials in these patients now that you know I think they are good trial candidates. And to you some novel immune-based regimens in this setting is I think really going to change some of the landscape for these patients.

This is a great session. Thank you all, I appreciate it.

Transcript Edited for Clarity