Opinion Statement
Despite early renal carcinoma diagnosis is more frequent nowadays, ~25–30 % of patients have metastatic disease at presentation and another ~30 % develop recurrent or metastatic disease after radical treatment for localized disease. In recent years, treatment of renal carcinoma is increasing in complexity due to the inclusion of a number of effective systemic treatments prolonging survival and increasing the therapeutic strategies for tumor debulking, or even achieving surgical complete responses and prolonged disease-free intervals. Initial multimodal approaches with immunotherapeutic agents are now being validated in patients treated with the new-targeted agents. Patients are now able to receive an optimal therapeutic strategy seeking a longer survival with an acceptable life quality and avoiding unnecessary comorbidities. In this context and as an initial therapeutic approach, it is imperative to promote patients’ selection with established prognostic models within a multidisciplinary team to assess the recommendation of a cytoreductive nephrectomy (CN), metastasectomy, and/or systemic treatment. In the context of mRCC, when feasible and in patients with favorable prognostic factors, the strategy should be to consider a CN or metastasectomy for tumor debulking in order to achieve free intervals of prolonged disease. By contrast, it is recommended to evaluate whether to perform a biopsy for histological diagnosis without nephrectomy in the following situations: high surgical risk, bulky metastatic disease or in specific sites (brain or liver) or ECOG PS 3/4. The following review covers from initial to recent studies on the integration of systemic treatment and surgery in the context of metastatic disease for an optimal multimodal management in renal carcinoma.
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Thillai K, Allan S, Powles T, Rudman S, Chowdhury S. Neoadjuvant and adjuvant treatment of renal cell carcinoma. Expert Rev Anticancer Ther. 2012;12(6):765–76.
Heng DYC, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. 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. 2009;27(34):5794–9. The authors present a prognostic model composed of six readily available clinical parameters that are able to stratify patients into favorable, intermediate and poor prognosis group.
Krabbe L-M, Haddad AQ, Westerman ME, Margulis V. Surgical management of metastatic renal cell carcinoma in the era of targeted therapies. World J Urol. 2014;32(3):615–22.
Tsao C-K, Small AC, Kates M, Moshier EL, Wisnivesky JP, Gartrell BA, et al. Cytoreductive nephrectomy for metastatic renal cell carcinoma in the era of targeted therapy in the United States: a SEER analysis. World J Urol. 2012;31(6):1535–9. The Surveillance, Epidemiology and End Results registry was used to identify patients with confirmed stage IV renal cell carcinoma between 2001 and 2008. The authors conclude that the use of cytoreductive nephrectomy in the United States has declined in the VEGFR-TKi era.
Culp SH, Tannir NM, Abel EJ, Margulis V, Tamboli P, Matin SF, et al. Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? Cancer [Internet]. 2010 May 17;116(14):3378–88. Available from: http://onlinewiley.papi.cph.es/store/10.1002/cncr.25046/asset/25046_ftp.pdf?v=1&t=hfba295e&s=51da39562b0a3d8faffc9d9719c3d46e30fb830c.
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 [Internet]. 2011 Jan;185(1):60–6. Available from: http://ac.els-cdn.com/S0022534710045489/1-s2.0-S0022534710045489-main.pdf?_tid=7ff8d004-9ee9-11e2-9d59-00000aab0f02&acdnat=1365273828_a8017b73bf2c73fdc429d750fd5adde3. In this retrospective analysis, cytoreductive nephrectomy was independently associated with a prolonged survival of patients with metastatic renal cell carcinoma treated with VEGFR-TKi agents.
Capitanio U, Abdollah F, Matloob R, Salonia A, Suardi N, Briganti A, et al. Effect of number and location of distant metastases on renal cell carcinoma mortality in candidates for cytoreductive nephrectomy: implications for multimodal therapy. Int J Urol. 2013;20:572–9.
Powles T, Blank C, Chowdhury S, Horenblas S, Peters J, Shamash J, et al. The outcome of patients treated with sunitinib prior to planned nephrectomy in metastatic clear cell renal cancer. Eur Urol. 2011;60(3):448–54. This article combined the data from two prospective phase 2 studies that assessed upfront sunitinib prior to nephrectomy in previously untreated patients with metastatic renal carcinoma. The results showed that upfront sunitinib prior to planned nephrectomy in intermediate-risk disease is associated with a median survival of>2 years.
Margulis V, Shariat SF, Rapoport Y, Rink M, Sjoberg DD, Tannir NM, et al. Development of accurate models for individualized predictionof survival after cytoreductive nephrectomy for metastatic renal cell carcinoma. Eur Urol. 2013;63:947–52.
Culp SH, Karam JA, Wood CG. Population-based analysis of factors associated with survival in patients undergoing cytoreductive nephrectomy in the targeted therapy era. Urologic Oncology: Seminars and Original Investigations. Elsevier; 2014 Apr 4:1–8.
Heng DYC, Wells JC, Rini BI, Beuselinck B, Lee J-L, 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 Eur Assoc Urol. 2014;26:1–7. In this retrospective analysis, authors found that most patients benefited from tumor removal, except for those with four o more Intenational Metastatic Renal Cell Carcinoma Database Consortium Risk Factors.
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;345:1655–9. Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal cell carcinoma than does interferon therapy alone in this prospective study. The authors believe that nephrectomy in suitable patients should be an elegibility criterion in trials of new systemic agents.
Mickisch GHJ, Garin A, Van Poppel H, Prijck L, Sylvester R. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001;358:966–70. This prospective study showed that radical nephrectomy before interferon-based immunotherapy might substantially delay time to progression and improve survival of patients with metastatic renal cell carcinoma who present with good performance status.
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;171:1071–6.
Krambeck AE, Leibovich BC, Lohse CM, Kwon ED, Zincke H, Blute ML. The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma. J Urol. 2006;176(5):1990–5.
Hutterer GC, Patard J-J, Colombel M, Belldegrun AS, Pfister C, Guille F, et al. Cytoreductive nephron-sparing surgery does not appear to undermine disease-specific survival in patients with metastatic renal cell carcinoma. Cancer. 2007;110(11):2428–33.
Capitanio U, Zini L, Perrotte P, Shariat SF, Jeldres C, Arjane P, et al. Cytoreductive partial nephrectomy does not undermine cancer control in metastatic renal cell carcinoma: a population-based study. Urology. 2008;72(5):1090–5.
Babaian KN, Merrill MM, Matin S, Tamboli P, Tannir NM, Jonasch E, et al. Partial nephrectomy in the setting of metastatic renal cell carcinoma. J Urol. Elsevier Ltd; 2014 Apr 28:1–7.
Walther MM, Lyne JC, Libutti SK, Linehan WM. Laparoscopic cytoreductive nephrectomy aspreparation for administration of systemic interleukin-2 in the treatment of metastatic renal cell carcinoma: a pilot study. Urology. 1999;53:496–501.
Finelli A, Kaouk JH, Fergany AF, Abreu SC, Novick AC, Gill IS. Laparoscopic cytoreductive nephrectomy for metastatic renal cell carcinoma. BJU Int. 2004;94:291–4.
Rabets JC, Kaouk JH, Fergany A, Finelli A, Gill IS, Novick AC. Laparoscopic versus open cytoreductive nephrectomy for metastatic renal cell carcinoma. Urology. 2004;64:930–4.
Matin SF, Madsen LT, Wood CG. Laparoscopic cytoreductive nephrectomy: the M. D. Anderson cancer center experience. J Urol. 2006;68:528–32.
Ganeshappa A, Sundaram C, Lerner MA, Gardner TA. Role of the laparoscopic approach to cytoreductive nephrectomy in metastatic renal-cell carcinoma: does size matter? J Endourol. 2010;24(8):1289–92.
Bin K Kroon, de Bruijn R, Prevoo W, Horenblas S, Powles T, Bex A. Oncology probability of downsizing primary tumors ofrenal cell carcinoma by targeted therapiesis related to size at presentation. Urology. Elsevier Inc; 2013 Jan 1;81(1):111–5.
Chapin BF, Delacroix SE Jr., Culp SH, Gonzalez GMN, Tannir NM, Jonasch E, et al. Safety of presurgical targeted therapy in the setting of metastatic renal cell carcinoma. Eur Urol [Internet]. 2011 Nov;60(5):964–71. Available from: http://ac.els-cdn.com/S0302283811005215/1-s2.0-S0302283811005215-main.pdf?_tid=e880fd0a-a4d8-11e2-a165-00000aacb361&acdnat=1365926409_8f153d3e2527df4da32afee726f08745.
Powles T, Kayani I, Blank C, Chowdhury S, Horenblas S, Peters J, et al. The safety and efficacy of sunitinib before planned nephrectomy in metastatic clear cell renal cancer. Ann Oncol [Internet]. 2011 Apr 26;22(5):1041–7. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082157/pdf/mdq564.pdf.
Bex A, Powles T. Selecting patients for cytoreductive nephrectomy in advanced renal cell carcinoma: who and when. Expert Rev Anticancer Ther. 2012;12(6):787–97.
Bex A, Haanen J. Do targeted agents offer clinical benefit as presurgical therapy? World J Urol. 2013;32(1):3–8.
Bigot P, Fardoun T, Bernhard JC, Xylinas E, Berger J, Rouprêt M, et al. Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful? World J Urol. 2013;32(1):109–14.
Abel EJ, Culp SH, Tannir NM, Tamboli P, Matin SF, Wood CG. Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib. Eur Urol. 2011;60(6):1273–9.
Kavolius JP, Mastarakos DP, Pavlovich C, Russo P, Burt ME, Brady MS. Resection of metastatic renal cell carcinoma. J Clin Oncol. 1998;16:2261–6.
Eggener SE, Yossepowitch O, Kundu S, Motzer RJ, Russo P. Risk score and metastasectomy independently impact prognosis of patients with recurrent renal cell carcinoma. J Urol. 2008;180(3):873–8.
Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Cancer. 2011;117(13):2873–82. The authors identified 887 patients who underwent nephrectomy for renal cell carcinoma who develop multiple metastatic lesions. The results indicated that complete resection of multiple RCC metastases may be associated with long-term survival and should be considered when technically feasible in appropriate surgical candidates.
Piltz S, Meimarakis G, Wichmann MW, Hatz R, Schildberg FW, Fuerst H. Long-term results after pulmonary resection of renal cell carcinoma metastases. Ann Thorac Surg. 2002;73:1082–7.
Renaud S, Falcoz PE, Alifano M, Olland A, Magdeleinat P, Pagès O, et al. Systematic lymph node dissection in lung metastasectomy of renal cell carcinoma: an 18 years of experience. J Surg Oncol. 2014;109(8):823–9.
Pfannschmidt J, Hoffmann H, Muley T, Krysa S, Trainer C, Dienemann H. Prognostic factors for survival after pulmonary resection of metastatic renal cell carcinoma. Ann Thorac Surg. 2002;74:1653–7.
Assouad J, Petkova B, Berna P, Dujon A, Foucault C, Riquet M. Renal cell carcinoma lung metastases surgery: pathologic findings and prognostic factors. Ann Thorac Surg Soc Thorac Surg. 2007;84(4):1114–20.
Murthy SC, Kim K, Rice TW, Rajeswaran J, Bukowski R, DeCamp MM, et al. Can we predict long-term survival after pulmonary metastasectomy for renal cell carcinoma? Ann Thorac Surg. 2005;79(3):996–1003.
Bigot P, Lebdai S, Ravaud A, Azzouzi A-R, Ferrière J-M, Patard J-J, et al. The role of surgery for metastatic renal cell carcinoma in the era of targeted therapies. World J Urol. 2013;31(6):1383–8.
Jung ST, Ghert MA, Harrelson JM, Scully SP. Management of osseous metastasis in renal carcinoma. Clin Orthop Relat Res. 2003;409:223–31.
Alves A, Adam R, Majno P, Delvart V, Azoulay D, Castaing D, et al. Hepatic resection for metastatic renal tumors: is it worthwhile? Ann Surg Oncol. 2003;10(6):705–10.
Thelen A, Jonas S, Benckert C, Lopez-Hänninen E, Rudolph B, Neumann U, et al. Liver resection for metastases from renal cell carcinoma. World J Surg. 2007;31(4):802–7.
Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, et al. Brain metastasis from renal cell carcinoma. Cancer. 2008;113(7):1641–8.
Tanis PJ, van der Gaag NA, Busch ORC, van Gulik TM, Gouma DJ. Systematic review of pancreatic surgery for metastatic renal cell carcinoma. Br J Surg. 2009;96(6):579–92.
Strobel O, Hackert T, Hartwig W, Bergmann F, Hinz U, Wente MN, et al. Survival data justifies resection for pancreatic metastases. Ann Surg Oncol. 2009;16(12):3340–9.
Zerbi A, Ortolano E, Balzano G, Borri A, Beneduce AA, Di Carlo V. Pancreatic metastasis from renal cell carcinoma: which patients benefit from surgical resection? Ann Surg Oncol. 2008;15(4):1161–8.
Iesalnieks I, Winter H, Bareck E, Sotiropoulos GC, Goretzki P, Klinhammer-Schalke M, et al. Thyroid metastases of renal cell carcinoma: clinical course in 45 patients undergoing surgery. Assessment of factors affecting patients’ survival. Thyroid. 2008;18(6):615–24.
Crispen PL, Blute ML. Role of cytoreductive nephrectomy in the Era of targeted therapy for renal cell carcinoma. Curr Urol Rep. 2011;13(1):38–46.
Richey SL, Culp SH, Jonasch E, Corn PG, Pagliaro LC, Tamboli P, et al. Outcome of patients with metastatic renal cell carcinoma treated with targeted therapy without cytoreductive nephrectomy. Ann Oncol [Internet]. 2011 Apr 26;22(5):1048–53. Available from: http://annonc.oxfordjournals.org/content/22/5/1048.full.pdf#page=1&view=FitH.
Zini L, Capitanio U, Perrotte P, Jeldres C, Shariat SF, Arjane P, et al. Population-based assessment of survival after cytoreductive nephrectomy versus no surgery in patients with metastatic renal cell carcinoma. Urology. 2009;73(2):342–6. Elsevier Inc. Elsevier Inc.
Aizer AA, Urun Y, McKay RR, Kibel AS, Nguyen PL, Choueiri TK. Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC). Br J Urol Int. 2014;113:E67–74.
Kim DY, Karam JA, Wood CG. Role of metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy. World J Urol. 2014;32(3):631–42.
Ljungberg B. The role of metastasectomy in renal cell carcinoma in the Era of targeted therapy. Curr Urol Rep. 2013;14:19–25.
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J. Puente Vasquez, T. Alonso Gordoa, J. Moreno, L. Poma, E. Diaz Rubio, A. Gomez, J. Blazquez, and JL Gonzalez Larriba declare that they have no conflict of interest.
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Puente Vázquez, J., Alonso Gordoa, T., Moreno, J. et al. New Challenges in Kidney Cancer Management: Integration of Surgery and Novel Therapies. Curr. Treat. Options in Oncol. 16, 13 (2015). https://doi.org/10.1007/s11864-015-0337-5
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DOI: https://doi.org/10.1007/s11864-015-0337-5