Cytoreductive Nephrectomy Retains Role in Modern RCC Era

James Wysock, MD

The primary research focus in renal cell carcinoma (RCC) may be on targeted and immunotherapy developments, but cytoreductive nephrectomy continues to be an effective treatment in patients with localized disease, says James Wysock, MD, adding that the approach could potentially be used to improve patient outcomes in advanced or metastatic disease.

“Cytoreductive nephrectomy works in the historical concept, and I don't think the modern era changes that. If you see someone with what looks like locally advanced disease, they should certainly be considered for evaluation for this approach,” said Wysock. “We have new minimally invasive techniques that can open up the avenue to patients who, in the past, may not have been good candidates for the surgery.”

Ongoing clinical trials are seeking to determine the role of the surgery. In SURTIME (EORTC 30073; NCT01099423), therapeutic sequencing was assessed. Patients were randomized to cytoreductive nephrectomy followed by sunitinib (Sutent) versus sunitinib followed by cytoreductive nephrectomy in the absence of metastatic disease progression.¹ There was no difference in progression-free rate 28 weeks, though results showed that the intent-to-treat population had an overall survival (OS) signal favoring deferred versus immediate cytoreductive nephrectomy. The median OS was 32.4 months (95% CI, 14.5-65.3) versus 15.1 months (95% CI 9.3-29.5), respectively (HR, 0.57; 95% CI, 0.34-0.95; P = .032).²

OncLive: Please provide an overview of your presentation.

What role does nephrectomy play in a landscape that already has several systemic agents?

What emerging techniques are there in the field?

What are some of the challenges or unanswered questions we have with cytoreductive nephrectomy?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Genitourinary Cancers, Wysock, who is chief of the urology service at NYC Health and Hospitals at Bellevue, and assistant professor in the Department of Urology, NYU Langone’s Perlmutter Cancer Center, discussed the evolution of cytoreductive nephrectomy in RCC.Wysock: I spoke about cytoreductive nephrectomy in what we call the modern era. Cytoreductive nephrectomy is a way of removing the tumor and taking out most of the cancer with the understanding that some will remain. Cytoreductive nephrectomy has been shown in a couple very well-designed and executed studies to improve OS. I addressed how that plays into the new era of targeted therapies, and I touched on how it may influence future management as the new generation of immunotherapy and immune checkpoint inhibitors start to enter the arena of RCC. Nephrectomy is the mainstay of local RCC treatment, but when we are talking about advanced or metastatic disease, the paradigm is still to include cytoreductive nephrectomy in the management. The question to ask is, “Who is the correct patient [for it]?” There's not as much data to determine whether targeted therapies or immune checkpoint inhibitors would have the same result, but there are early data to suggest that they’re providing similar OS benefits. There is a whole new realm of neoadjuvant treatments with these therapies that may also open up new avenues of therapy for patients with disease that may appear to be unresectable, but can be resectable. Similarly, diseases that may be complex to manage with a partial nephrectomy and a neoadjuvant treatment regimen can be supplemented with a nephron-sparing approach.We have been employing and increasing our use of robotics and minimally invasive approaches toward managing more advanced disease around the kidney. We are taking on the more complex partial nephrectomies with robotic and minimally invasive approaches, but in the setting of a cytoreductive nephrectomy and an inferior vena cava tumor thrombus for an advanced disease. That’s a realm in which there are more options for using robotic and minimally invasive approaches. This offers a lower morbidity for the patients. Some of the poorer-risk patients who would ordinarily get supportive care may be candidates for these minimally invasive, cytoreductive treatments.The crux of the question is whether or not it works in the current treatment paradigm. We believe it does, but there are 2 ongoing trials—the SURTIME and the CARMENA prospective randomized trials using sunitinib that are trying to answer whether or not cytoreductive nephrectomy will show the same OS benefit in this setting. They have had a lot of trouble accruing patients, and they're about 6 years behind their originally designed endpoint.

Is that the foundational problem—not enough education and awareness?

Are there other exciting neoadjuvant clinical trials that are ongoing?

That’s a major challenge, and likely will continue to be a major challenge for future studies looking to address the same questions with immune checkpoint inhibitors. In order to overcome this, we have to provide more education to surgeons and physicians as to how best explain these trials to patients and their possible benefits. There is always a challenge in randomizing people in a surgical trial. Being told that the surgery might help improve your OS, but that you are going to be randomized to an arm that doesn't include surgery is very challenging to convince people to enroll in. The very nature of a randomized surgical trial presents challenges for accrual. It’s difficult and it requires a very well-thought-out explanation to patients.There are ongoing neoadjuvant trials. As the number of agents continues to explode faster than the trials can be designed and implemented, I’m excited to see the data showing their effectiveness. In time, we will have more trials designed to show improvement. There is [one clinical trial] that is looking at the use of axitinib (Inlyta) to decrease the size of tumors and open up the opportunity to do nephron-sparing surgery for people with locally advanced disease. We'll see, as that design rolls out and increases accrual, [if it will provide] new avenues for patients.

References

1. Bex, Axel, Ljungberg, Borje, Poppel, Hein van, et al. The role of cytoreductive nephrectomy: European association of urology recommendations in 2016. Eur Urol. 2016;70(5):901-905. doi: 10.1016/j.eururo.2016.07.005.
2. Bex A, Mulders P, Jewett M, et al. Immediate versus deferred cytoreductive nephrectomy (CN) in patients with synchronous metastatic renal cell carcinoma (mRCC) receiving sunitinib (EORTC 30073 SURTIME). In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract LBA35.