Is Cytoreductive Nephrectomy Still a Standard of Care in Metastatic Renal Cell Carcinoma?

Main Article Content

Alex Renner
Suraj Samtani
Arnaldo Marín
Mauricio Burotto

Keywords

cytoreductive nephrectomy, immunotherapy, metastatic renal cell carcinoma, sunitinib, surgical outlook

Abstract

Cytoreductive nephrectomy has been an integral part of management in metastatic renal cell carcinoma for patients with good performance status, based on the benefit shown by prospective trials in the interferon era and retrospective trials in the targeted therapies era. Clinical Trial to Assess the Importance of Nephrectomy (CARMENA), the first prospective phase III trial comparing a targeted agent alone (sunitinib) versus nephrectomy plus sunitinib, has been recently published, showing non-inferiority for the nephrectomy-sparing arm. In this article, we discuss the impact of nephrectomy including its immune-mediated effects, surgical morbidity and mortality, and the clinical data supporting the indications of nephrectomy in order to analyze the CARMENA trial in context, with the aim to identify optimal strategies for different patient populations in the metastatic setting.

Abstract 2236 | PDF Downloads 1317 HTML Downloads 951 XML Downloads 779

References

1. Stewart B, Wild C. International Agency for Research on Cancer, WHO. World cancer report 2014 [Internet]. [cited 2019 Jan 20]. Available from: http://www.thehealthwell.info/node/725845
2. Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, et al. SEER cancer statistics review, 1975–2015. National Cancer Institute [Internet]. [cited 2019 Jan 20]. Available from: https://seer.cancer.gov/csr/1975_2015/
3. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115–24. http://dx.doi.org/10.1056/NEJMoa065044
4. 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 Dec 6;345(23):1655–9. http://dx.doi.org/10.1056/NEJMoa003013
5. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: A randomised trial. Lancet. 2001 Sep 22;358(9286):966–70. http://dx.doi.org/ 10.1016/S0140-6736(01)06103-7
6. Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: A combined analysis. J Urol. 2004 Mar;171(3):1071–6. http://dx.doi.org/10.1097/01.ju.0000110610.61545.ae
7. Lahn M, Fisch P, Köhler G, Kunzmann R, Hentrich I, Jesuiter H, et al. Pro-inflammatory and T cell inhibitory cytokines are secreted at high levels in tumor cell cultures of human renal cell carcinoma. Eur Urol. 1999 Jan;35(1):70–80. http://dx.doi.org/ 10.1159/000019821
8. Uzzo RG, Rayman P, Kolenko V, Clark PE, Bloom T, Ward AM, et al. Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin Cancer Res. 1999 May;5(5):1219–29.
9. Xia Y, Zhang Q, Zhen Q, Zhao Y, Liu N, Li T, et al. Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway. Oncotarget. 2017 Jun 6;8(23):37783–95. http://dx.doi.org/10.18632/oncotar-get. 16354
10. Dadian G, Riches PG, Henderson DC, Taylor A, Moore J, Atkinson H, et al. Immunological parameters in peripheral blood of patients with renal cell carcinoma before and after nephrectomy. Br J Urol. 1994 Jul;74(1):15–22. http://dx.doi.org/10.1111/j.1464-410X.1994.tb16538.x
11. Eruslanov E, Stoffs T, Kim WJ, Daurkin I, Gilbert SM, Su LM, et al. Expansion of CCR8(+) inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas. Clin Cancer Res. 2013 Apr 1;19(7):1670–80. http://dx.doi.org/10.1158/1078-0432.CCR-12-2091
12. Larkin J. A study of anti-PD1 (Nivolumab) therapy as pre- and post-operative therapy in metastatic renal cell cancer (ADAP-TeR). ClinicalTrials.gov Identifier: NCT02446860 [Internet]. [cited 2019 Jan 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02446860
13. Gatenby RA, Gawlinski ET, Tangen CM, Flanigan RC, Craw-ford ED. The possible role of postoperative azotemia in enhanced survival of patients with metastatic renal cancer after cytoreductive nephrectomy. Cancer Res. 2002 Sep 15;62(18):5218–22.
14. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. CheckMate 214 investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277–90. http://dx.doi.org/10.1056/NEJMoa1712126
15. Flanigan RC. The failure of infarction and/or nephrectomy in stage IV renal cell cancer to influence survival or metastatic regression. Urol Clin North Am. 1987 Nov;14(4):757–62.
16. Onishi T, Machida T, Masuda F, Kurauchi H, Mori Y, Suzuki M, et al. Nephrectomy in renal carcinoma with distant metastasis. Br J Urol. 1989 Jun;63(6):600–4. http://dx.doi.org/10.1111/j. 1464-410X.1989.tb05253.x
17. Conti SL, Thomas IC, Hagedorn JC, Chung BI, Chertow GM, Wagner TH, et al. Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era. Int J Cancer. 2014 May 1;134(9):2245–52. http://dx.doi.org/10.1002/ijc.28553
18. Silberstein JL, Adamy A, Maschino AC, Ehdaie B, Garg T, Favaretto RL. Systematic classification and prediction of complications after nephrectomy in patients with metastatic renal cell carcinoma (RCC). BJU Int. 2012 Nov;110(9):1276–82. http://dx.doi.org/10.1111/j.1464-410X.2012.11103.x
19. Abdollah F, Sun M, Thuret R, Schmitges J, Shariat SF, Perrotte P, et al. Mortality and morbidity after cytoreductive nephrectomy for metastatic renal cell carcinoma: A population-based study. Ann Surg Oncol. 2011;18, 2988–96. http://dx.doi.org/10.1245/s10434-011-1715-2
20. Wallis CJ, Bjarnason G, Byrne J, Cheung DC, Hoffman A, Kulkarni GS, et al. Morbidity and mortality of radical nephrectomy for patients with disseminated cancer: An analysis of the National Surgical Quality Improvement Program database. Urology. 2016 Sep;95:95–102. http://dx.doi.org/10.1016/j.urology.2016.04.055
21. Cloutier V, Capitanio U, Zini L, Perrotte P, Jeldres C, Shariat SF, et al. Thirty-day mortality after nephrectomy: Clinical implications for informed consent. Eur Urol. 2009 Dec;56(6):998–1003. http://dx.doi.org/10.1016/j.eururo.2008.11.023
22. Sun M, Abdollah F, Schmitges J, Bianchi M, Tian Z, Shariat SF, et al. Cytoreductive nephrectomy in the elderly: A population-based cohort from the USA. BJU Int. 2012 Jun;109(12):1807–12. http://dx.doi.org/10.1111/j.1464-410X.2011.10569.x
23. You D, Jeong IG, Song C, Lee JL, Hong B, Hong JH, et al. Analysis of preoperative variables for identifying patients who might benefit from upfront cytoreductive nephrectomy for metastatic renal cell carcinoma in the targeted therapy era. Jpn J Clin Oncol. 2015 Jan;45(1):96–102. http://dx.doi.org/10.1093/jjco/hyu171
24. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8): 2530–40. http://dx.doi.org/10.1200/JCO.1999.17.8.2530
25. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722–31. http://dx.doi.org/10.1056/NEJMoa1303989
26. Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): Final analysis of overall survival. J Clin Oncol. 2010 May 1;28(13):2144–50. http://dx.doi.org/10.1200/JCO.2009.26.7849
27. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22): 2271–81. http://dx.doi.org/10.1056/NEJMoa066838
28. Hanna N, Sun M, Meyer CP, Nguyen PL, Pal SK, Chang SL, et al. Survival analyses of patients with metastatic renal cancer treated with targeted therapy with or without cytoreductive nephrectomy: A national cancer database study. J Clin Oncol. 2016 Sep 20;34(27):3267–75. http://dx.doi.org/10.1200/JCO.2016.66.7931
29. Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol. 2014 Oct;66(4):704–10. http://dx.doi.org/10.1016/j.eururo.2014.05.034
30. Abern MR, Scosyrev E, Tsivian M, Messing EM, Polascik TJ, Dudek AZ. Survival of patients undergoing cytoreductive surgery for metastatic renal cell carcinoma in the targeted- therapy era. Anticancer Res. 2014 May;34(5):2405–11.
31. Bex A, Mulders P, Jewett M, Wagstaff J, van Thienen JV, Blank CU, et al. Immediate versus deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib. Ann Oncol. 2017;28( suppl 5): v605–49. http://dx.doi.org/10.1093/annonc/mdx440.030
32. Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, et al. Sunitinib alone or after nephrectomy in metastatic re-nal-cell carcinoma. N Engl J Med. 2018 Aug 2;379(5):417–27. http://dx.doi.org/10.1056/NEJMoa1803675
33. 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 Jan;185(1):60–6. http://dx.doi.org/10.1016/j.juro.2010.09.012
34. Motzer R. Powles T, Atkins M, Escudier B, McDermott D, Suarez C, et al. IMmotion 151: Randomized phase III study of atezolizumab plus bevacizumab versus sunitinib in untreated metastatic renal cell carcinoma. J Clin Oncol. 2018;36 (suppl, 578).
35. Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, et al. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: A non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018 Mar;19(3):405–15. http://dx.doi.org/10.1016/S1470-2045(18)30081-0