What is cytoreductive nephrectomy’s current role in RCC treatment?

The introduction of targeted therapies and immunotherapies has generated uncertainty regarding the role of the cytoreductive nephrectomy in the treatment of metastatic renal cell carcinoma. In this interview, Hyung L. Kim, MD, of Cedars Sinai Medical Center, Los Angeles, discusses the recent CARMENA and SURTIME clinical trials, and outlines the upcoming SWOG-1931 trial.

What is the current rationale for using cytoreductive nephrectomy in patients with metastatic renal cell carcinoma?

Since the interferon era, a lot of treatments have been approved. They include targeted therapies and immunotherapies. It's not clear what the role of cytoreduction is in the modern era with modern therapies. Two recent studies highlight the controversy. CARMENA was a study that randomized patients to surgery or no surgery prior to receiving sunitinib (Sutent). In this study, the survival was similar in the two arms, suggesting that cytoreduction should not be performed.

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SURTIME was a study conducted by EORTC, which is a European cooperative group. They compared immediate cytoreduction at the time of diagnosis to deferred cytoreduction after starting sunitinib for metastatic renal cell carcinoma. This trial closed early, so any observations are only hypothesis generating. However, in this study, the overall survival was much longer for patients undergoing deferred nephrectomy when compared to immediate nephrectomy.

To summarize the results of these two trials, CARMENA shows that there's no difference between immediate nephrectomy and no nephrectomy, and SURTIME suggests that there's a signal where deferred nephrectomy has better survival than immediate nephrectomy.

What do you hope to learn from the SWOG-1931 trial?

SWOG-1931 is a concept that has been approved for development by the NIH. We hope to have this study activated and available for cooperative groups to open in the summer of 2020. The study compares deferred nephrectomy, similar to what was studied in SURTIME, to no nephrectomy. The study has two registration steps. Patients with newly diagnosed metastatic renal cell carcinoma can be registered and treated with a combination therapy that includes at least one checkpoint inhibitor, so they initially undergo systemic therapy. If you have a complete response or progressive disease, you're off the study because you're unlikely to benefit from surgery. However, if you have a partial response or if you have stable disease, then you're randomized to either cytoreductive nephrectomy or no nephrectomy.

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We hope to understand the role of cytoreductive nephrectomy and patients whose disease is stable or having some response to an immunotherapy-based combination regimen.