AUA 2022: Is Cytoreductive Nephrectomy Dead or Alive in 2022?

(UroToday.com) The 2022 American Urological Association (AUA) Annual Meeting included the Society of Urologic Oncology (SUO) session and a presentation by Dr. Daniel Shapiro discussing the role of cytoreductive nephrectomy in 2022. From a historical perspective, Dr. Shapiro notes that in a combined analysis of SWOG 8949 and EORTC 30947, the median overall survival for cytoreductive nephrectomy + IFN-alpha was 13 months and for IFN-alpha alone was 7.8 months (p = 0.001). Benefits of cytoreductive nephrectomy include improved survival, and can also be important for symptomatic/palliative reasons. Of note, among all of the systemic therapy trials for metastatic RCC, the majority of patients had a prior nephrectomy:

 

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 Published in 2018,1 the CARMENA trial questioned the utility of cytoreductive nephrectomy. CARMENA randomized patients 1:1 to undergo nephrectomy and then receive sunitinib or to receive sunitinib alone. At the planned interim analysis, the median follow-up was 50.9 months, and the results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (HR for death 0.89, 95% CI 0.71-1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The SURTIME trial assessed immediate surgery or surgery after sunitinib in treating patients with metastatic RCC. The intention-to-treat OS HR of deferred vs immediate cytoreductive nephrectomy was 0.57 (95% CI, 0.34-0.95; p = 0.03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred cytoreductive nephrectomy arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate cytoreductive nephrectomy arm. However, Dr. Shapiro notes that there were several limitations with the CARMENA trial, including (i) the under accrual of 450 patients (of a planned 576), (ii) 44% of patients being poor risk, and (iii) 7% of patients randomized to nephrectomy + sunitinib not undergoing a nephrectomy. In a deeper dive into the data from CARMENA, there were several predictors of worse OS:

  • Node positive (35% of patients in CARMENA)
  • Bone metastasis (36% of patients in CARMENA)
  • cT3-T4 disease (70% in the surgery arm and 51% in the sunitinib arm of CARMENA)

 

To further highlight that CARMENA selected poor risk patients, it is important to look at the median overall survival in the sunitinib arm. In CARMENA this was 18.4 months, whereas if we look at other prior phase III trials, this ranges from 26.4 to 40 months:

 

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 Dr. Shapiro emphasized that it is important to integrate cytoreductive nephrectomy with modern systemic therapy. Looking at the most recent updated follow-up from CheckMate 214, the median overall survival is 56 months for nivolumab + ipilimumab. Similarly, with extended follow-up of KEYNOTE-426, the median survival for pembrolizumab + axitinib is 46 months.

 

Ultimately, the selection of patients for cytoreductive nephrectomy is likely multifactorial, including tumor, patient, and health care system factors:

  • Tumor: presence of tumor thrombus, presence of sarcomatoid dedifferentiation, primary tumor volume, and metastatic number and location
  • Patient: prognostic scores (IMDC/MDACC), performance status, and symptoms
  • Health care system: hospital volume, multidisciplinary team, and patient access

 

With regards to ongoing cytoreductive nephrectomy clinical trials, Dr. Shapiro highlighted the NORDIC-SUN and SWOG1931 “PROBE” trials, both of which only allow deferred cytoreductive nephrectomy:

 

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Dr. Shapiro concluded his presentation by discussing the role of cytoreductive nephrectomy in 2022 with the following future directions:

  • Surgeons must ask themselves who and when to perform a cytoreductive nephrectomy and why does it work?
  • We need prospective, multi-institutional studies that include upfront cytoreductive nephrectomy
  • If we don’t answer the surgical questions, on one will

 

Presented By: Daniel Shapiro, MD, University of Wisconsin, Madison, WI

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

References:

  1. Mejean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal cell carcinoma. N Engl J Med 2018 Aug 2;379(5):417-427.

 

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