MDACC 2018: Debate: Is There Still a Role for Cytoreductive Nephrectomy in the Setting of Metastatic Renal Cell Carcinoma?

Houston, TX ( Dr. Karam started out reviewing trials from the pre-targeted therapy era opening with the results of the EORTC trial comparing cytoreductive nephrectomy (CN) plus interferon-alpha versus interferon alpha alone1.

This study demonstrated a survival benefit of 10 months in patients that underwent CN plus interferon-alpha versus interferon alpha alone.  In the SWOG trial evaluating nephrectomy followed by interferon alpha-2b compared with interferon alpha-2b alone, the median survival of CN followed by interferon was 11.1 months compared to 8.1 months with interferon alone (p=0.05)2.  What about the role of CN in the targeted era?  A retrospective study demonstrated that CN prior to treatment with anti-VEGF therapy (Sunitinib, Sorafenib or Bevacizumab) was independently associated with a prolonged OS in those with good performance status and if they were not considered poor risk by MSKCC criteria3. There are two prospective trials addressing CN in mRCC, the SURTIME trial and CARMENA trial 4.  In the SURTIME trial, surgery followed by Sunitinib versus Sunitinib followed by surgery was compared.  Only 99 patients could be accrued.  In the intention to treat group, there was no difference in PFS, but the final results are still awaiting publication.  In the CARMENA trial, nephrectomy followed by Sunitinib versus Sunitinib alone was compared.  Again, there was no difference in OS or PFS.  However, Dr. Karam pointed out several issues with this study.   In the nephrectomy group, 7% never had surgery and 17% never received Sunitinib.  In the Sunitinib only group, 4.9% never received Sunitinib and 17% ended up having surgery.  Additionally, ~30 patients per year underwent CN, so the experience is limited in these centers, which may affect outcomes.  Finally, perhaps in the immunotherapy era, since Nivo/Ipi is approved for first-line therapy in mRCC, the CARMENA results may no longer be relevant. Dr. Karam concluded that in well-selected patients, CN is associated with longer survival and should be considered.   

In addition to the CARMENA trial results, Dr. Jonasch also took on a more basic science mechanistic approach to explain why it would be wise to avoid CN in the setting of mRCC.  He explained the benefits of leaving the primary tumor in situ in order to “train the T cells” to combat tumor cells.   He provided a clinical example of a 63-year-old female who presented with a large renal mass and multiple lung nodules.  Biopsy revealed clear cell RCC with sarcomatoid differentiation.  The patient underwent Nivo/Bevacizumab with significant clinical improvement.  CT scan demonstrated that the lung nodules decreased significantly and the only residual disease was the renal mass, IVC thrombus, and a retroperitoneal mass.  She eventually underwent a surgery with the final pathology of the kidney with necrosis and demonstrating no sarcomatoid features and continues to do well.   This is an example where upfront surgery for her complex metastatic kidney cancer would have been very complicated with significant morbidity.   leaving the tumor in situ may help train T cells to attack the tumor and there may be a role for CN, but not necessarily up front.  If the patient responds to systemic therapy, then consideration of the removal of primary should be considered at some point.

Presented by: Jose A. Karam, MD, Associate Professor of Urologic Oncology, (Pro), and Eric Jonasch, MD, Professor of Genitourinary Medical Oncology, (Con), MD Anderson Cancer Center, Houston, TX, USA

Written by Dr. Amy H. Lim, MD, PhD, Urologic Oncology Fellow and Ashish M. Kamat, MD, (@UroDocAsh), Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 13th Update on the Management of Genitourinary Malignancies, The University of Texas (MDACC - MD Anderson Cancer Center) November 9-10, 2018, Dan L. Duncan Building, Houston, TX

1. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R, Group EOfRaToCEG. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001;358(9286):966-70.
2. Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001;345(23):1655-9.
3. Choueiri TK, Xie W, Kollmannsberger C, North S, Knox JJ, Lampard JG, et al. The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol. 2011;185(1):60-6.
4.  Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018;379(5):417-27.