Abstract
Background
Cytoreductive nephrectomy (CN) has been considered standard management for patients with metastatic renal cell carcinoma (mRCC) for over a decade. This practice, based on evidence from the immunotherapy era, has now come into question with the dramatic shift in management of mRCC patients due to the development and approval of several targeted molecular therapies (TMT).
Methods
A comprehensive English language literature review was performed using MEDLINE/PubMed to identify articles and guidelines pertinent to CN in mRCC.
Results
Retrospective studies have demonstrated improved survival for patients who underwent CN compared to those that did not; however, these studies suffer from heavy selection bias. Furthermore, the optimal timing of TMT, before or after surgery is not known. Pre-surgical TMT has the advantage of early treatment of metastases, downsizing of the primary, and may be an effective ‘litmus test’ for the selection of patients for CN based on response to TMT. The results of two ongoing phase III trials (CARMENA and SURTIME) will address much of the controversy on the role of CN and the timing of systemic therapy in the TMT era. In this review, we aim to present the evidence that lead to adoption of CN in the era of immunotherapies as well as the available data about the oncologic benefit of CN in patients with mRCC who receive TMT as their primary systemic therapy.
Conclusion
There seems to be an important role for CN in the era of TMT, mostly in patients with favorable risk and where a high percentage of tumor burden can be removed by cytoreductive surgery.
Similar content being viewed by others
References
Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30
Lam JS, Leppert JT, Belldegrun AS, Figlin RA (2005) Novel approaches in the therapy of metastatic renal cell carcinoma. World J Urol 23:202–212
Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C (2008) Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 34:193–205
Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC et al (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345:1655–1659
Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358:966–970
Clinical trial to assess the importance of nephrectomy (CARMENA). US National Institute of Health website
Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME)
van der Veldt AA, Meijerink MR, van den Eertwegh AJ, Bex A, de Gast G, Haanen JB et al (2008) Sunitinib for treatment of advanced renal cell cancer: primary tumor response. Clin Cancer Res 14:2431–2436
Abel EJ, Culp SH, Tannir NM, Tamboli P, Matin SF, Wood CG (2011) Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib. Eur Urol 60:1273–1279
Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED (2004) Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 171:1071–1076
Walther MM, Alexander RB, Weiss GH, Venzon D, Berman A, Pass HI et al (1993) Cytoreductive surgery prior to interleukin-2-based therapy in patients with metastatic renal cell carcinoma. Urology 42:250–257 (discussion 7–8)
Fallick ML, McDermott DF, LaRock D, Long JP, Atkins MB (1997) Nephrectomy before interleukin-2 therapy for patients with metastatic renal cell carcinoma. J Urol 158:1691–1695
Sun M, Abdollah F, Schmitges J, Bianchi M, Tian Z, Shariat SF et al (2012) Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA. BJU Int 109:1807–1812
Marcus SG, Choyke PL, Reiter R, Jaffe GS, Alexander RB, Linehan WM et al (1993) Regression of metastatic renal cell carcinoma after cytoreductive nephrectomy. J Urol 150:463–466
Wagner JR, Walther MM, Linehan WM, White DE, Rosenberg SA, Yang JC (1999) Interleukin-2 based immunotherapy for metastatic renal cell carcinoma with the kidney in place. J Urol 162:43–45
Lara PN Jr, Tangen CM, Conlon SJ, Flanigan RC, Crawford ED (2009) Predictors of survival of advanced renal cell carcinoma: long-term results from Southwest Oncology Group Trial S8949. J Urol 181:512–516 (discussion 6–7)
Tsao CK, Small AC, Kates M, Moshier EL, Wisnivesky JP, Gartrell BA et al (2013) Cytoreductive nephrectomy for metastatic renal cell carcinoma in the era of targeted therapy in the United States: a SEER analysis. World J Urol 31:1535–1539
Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590
Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124
Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068
Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS et al (2008) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26:5422–5428
Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281
Powles T, Kayani I, Blank C, Chowdhury S, Horenblas S, Peters J et al (2011) The safety and efficacy of sunitinib before planned nephrectomy in metastatic clear cell renal cancer. Ann Oncol 22:1041–1047
Abel EJ, Culp SH, Tannir NM, Matin SF, Tamboli P, Jonasch E et al (2011) Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma. Eur Urol 59:10–15
Conti SL, Thomas IC, Hagedorn JC, Chung BI, Chertow GM, Wagner TH, et al. (2014) Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era. Int J Cancer 134(9):2245–2252
Choueiri TK, Xie W, Kollmannsberger C, North S, Knox JJ, Lampard JG et al (2011) The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol 185:60–66
Richey SL, Culp SH, Jonasch E, Corn PG, Pagliaro LC, Tamboli P et al (2011) Outcome of patients with metastatic renal cell carcinoma treated with targeted therapy without cytoreductive nephrectomy. Ann Oncol 22:1048–1053
Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540
Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296
Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799
Heng DY, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN et al (2013) External validation and comparison with other models of the international metastatic renal-cell carcinoma database consortium prognostic model: a population-based study. Lancet Oncol 14:141–148
Culp SH, Tannir NM, Abel EJ, Margulis V, Tamboli P, Matin SF et al (2010) Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? Cancer 116:3378–3388
Shuch B, Said J, La Rochelle JC, Zhou Y, Li G, Klatte T et al (2009) Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology—is up-front resection indicated and, if not, is it avoidable? J Urol 182:2164–2171
Kassouf W, Sanchez-Ortiz R, Tamboli P, Tannir N, Jonasch E, Merchant MM et al (2007) Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology. J Urol 178:1896–1900
Kroeger N, Xie W, Lee JL, Bjarnason GA, Knox JJ, Mackenzie MJ et al (2013) Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: characterization of survival outcome and application of the international mRCC database consortium criteria. Cancer 119:2999–3006
Chittoria N, Zhu H, Choueiri TK, Kroeger N, Lee J-L, Srinivas S, et al (2013) Outcome of metastatic sarcomatoid renal cell carcinoma (sRCC): results from the International mRCC database consortium. ASCO meeting abstracts. 31:4565
Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S et al (2008) Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol 26:127–131
Pierorazio PM, McKiernan JM, McCann TR, Mohile S, Petrylak D, Benson MC (2007) Outcome after cytoreductive nephrectomy for metastatic renal cell carcinoma is predicted by fractional percentage of tumour volume removed. BJU Int 100:755–759
Barbastefano J, Garcia JA, Elson P, Wood LS, Lane BR, Dreicer R et al (2010) Association of percentage of tumour burden removed with debulking nephrectomy and progression-free survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. BJU Int 106:1266–1269
Iacovelli R, Lanoy E, Albiges L, Escudier B (2012) Tumour burden is an independent prognostic factor in metastatic renal cell carcinoma. BJU Int 110:1747–1753
Margulis V, Wood CG (2009) Pre-surgical targeted molecular therapy in renal cell carcinoma. BJU Int 103:150–153
Rini BI, Garcia J, Elson P, Wood L, Shah S, Stephenson A et al (2012) The effect of sunitinib on primary renal cell carcinoma and facilitation of subsequent surgery. J Urol 187:1548–1554
Ficarra V, Novara G (2010) Kidney cancer: neoadjuvant targeted therapies in renal cell carcinoma. Nat Rev Urol 7:63–64
Kroon BK, de Bruijn R, Prevoo W, Horenblas S, Powles T, Bex A (2013) Probability of downsizing primary tumors of renal cell carcinoma by targeted therapies is related to size at presentation. Urology 81:111–115
Yuasa T, Urakami S, Yamamoto S, Yonese J, Nakano K, Kodaira M et al (2011) Tumor size is a potential predictor of response to tyrosine kinase inhibitors in renal cell cancer. Urology 77:831–835
Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E (1999) Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 103:159–165
Cost NG, Delacroix SE Jr, Sleeper JP, Smith PJ, Youssef RF, Chapin BF et al (2011) The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus. Eur Urol 59:912–918
Bex A, Horenblas S, Meinhardt W, Verra N, de Gast GC (2002) The role of initial immunotherapy as selection for nephrectomy in patients with metastatic renal cell carcinoma and the primary tumor in situ. Eur Urol 42:570–574 (discussion 5–6)
Wood CG (2007) Multimodal approaches in the management of locally advanced and metastatic renal cell carcinoma: combining surgery and systemic therapies to improve patient outcome. Clin Cancer Res 13:697s–702s
Shaw GL, Hussain M, Nair R, Bycroft J, Beltran L, Green JS et al (2012) Performing cytoreductive nephrectomy following targeted sunitinib therapy for metastatic renal cell carcinoma: a surgical perspective. Urol Int 89:83–88
Margulis V, Matin SF, Tannir N, Tamboli P, Swanson DA, Jonasch E et al (2008) Surgical morbidity associated with administration of targeted molecular therapies before cytoreductive nephrectomy or resection of locally recurrent renal cell carcinoma. J Urol 180:94–98
Chapin BF, Delacroix SE Jr, Culp SH, Nogueras Gonzalez GM, Tannir NM, Jonasch E et al (2011) Safety of presurgical targeted therapy in the setting of metastatic renal cell carcinoma. Eur Urol 60:964–971
Jonasch E, Wood CG, Matin SF, Tu SM, Pagliaro LC, Corn PG et al (2009) Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma. J Clin Oncol 27:4076–4081
Bex A, Jonasch E, Kirkali Z, Mejean A, Mulders P, Oudard S et al (2010) Integrating surgery with targeted therapies for renal cell carcinoma: current evidence and ongoing trials. Eur Urol 58:819–828
Powles T, Sarwar N, Stockdale A, Boleti E, Jones RJ, Protheroe A, et al (2013) Pazopanib prior to planned nephrectomy in metastatic clear cell renal cancer: a clinical and biomarker study. ASCO meeting abstracts. 31:4508
Bex A, Haanen J (2014) Do targeted agents offer clinical benefit as presurgical therapy? World J Urol 32:3–8
Conflict of interest
The authors declare that there are no financial disclosures or conflict of interest regarding this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Krabbe, LM., Haddad, A.Q., Westerman, M.E. et al. Surgical management of metastatic renal cell carcinoma in the era of targeted therapies. World J Urol 32, 615–622 (2014). https://doi.org/10.1007/s00345-014-1286-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00345-014-1286-5