Skip to main content

Advertisement

Log in

The Role of Metastasectomy in Renal Cell Carcinoma in the Era of Targeted Therapy

  • Kidney Diseases (G Ciancio, Section Editor)
  • Published:
Current Urology Reports Aims and scope Submit manuscript

Abstract

Despite contemporary innovations in systemic therapy and surgical treatment, renal cell carcinoma (RCC) remains the most lethal urologic malignancy. Still, around 20 % of patients with RCC present with metastases at diagnosis, and 40–50 % of those with localized advanced disease will ultimately progress to metastatic disease. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Searches were carried out in the PubMed database and the Cochrane Library of Controlled Clinical Trials. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy. In multivariate analysis, independent predictive factors included male gender, disease-free interval > 1 year, single metastatic site and complete metastasectomy. Other reports from selected patient materials show 29–31 % 5-year overall survival rates. In patients with recurrent disease after resection of a lung metastasis, 60 % were able to undergo a subsequent resection, compared with 25 % with recurrent bone metastasis. Also, metastasectomy after initial systemic therapy gave partial or complete response in a majority of patients. In these patients, the median survival was 4.7 years and 21 % remained free of disease at last follow-up. Patients with metastatic renal cell carcinoma should be considered for multimodal therapy, including surgery of metastatic lesions. A proportion of patients will achieve long-term survival with aggressive surgical resection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Flanigan RC, Campbell SC, Clark JI, Picken MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003;4(5):385–90.

    Article  PubMed  Google Scholar 

  2. Swanson DA. Surgery for metastases of renal cell carcinoma. Scand J Surg. 2004;93:150–5.

    PubMed  CAS  Google Scholar 

  3. Ljungberg B, Landberg G, Alamdari FI. Factors of importance for prediction of survival in patients with metastatic renal cell carcinoma, treated with or without nephrectomy. Scand J Urol Nephrol. 2000;34:246–51.

    Article  PubMed  CAS  Google Scholar 

  4. •• Coppin C, Kollmannsberger C, Le L, Porzsolt F, Wilt TJ. Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials. BJU Int 2011;108:1556–63. In this Cochrane systematic review, it was concluded that agents targeting VEGF and mTOR pathways improve PFS in both first-line and second-line settings. The authors found that the treatments rarely yield complete responses and thus are not curative. However, no placebo-controlled trial has reported a health-related quality of life benefit.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  Google Scholar 

  6. Kwan KG, Kapoor A. Cytoreductive nephrectomy in metastatic renal cell carcinoma: the evolving role of surgery in the era of molecular targeted therapy. Curr Opin Support Palliat Care. 2009;3:157–65.

    Article  PubMed  Google Scholar 

  7. •• Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, Patard JJ, Mulders PF, Sinescu IC. EAU guidelines on renal cell carcinoma: the 2010 update European Association of Urology Guideline Group. Eur Urol. 2010;58:398–406. Evidence-based guidelines with recommendations for the treatment of an individual patient with renal cell carcinoma, according to a current standardized general approach.

    Article  PubMed  Google Scholar 

  8. Russo P, Synder M, Vickers A, Kondagunta V, Motzer R. Cytoreductive nephrectomy and nephrectomy/complete metastasectomy for metastatic renal cancer. Sci World J. 2007;7:768–78.

    Article  Google Scholar 

  9. Russo P. Multi-modal treatment for metastatic renal cancer: the role of surgery. World J Urol. 2010;28(3):295–301.

    Article  PubMed  Google Scholar 

  10. van der Poel HG, Roukema JA, Horenblas S, van Geel AN, Debruyne FM. Metastasectomy in renal cell carcinoma: A multicenter retrospective analysis. Eur Urol. 1999;35(3):197–203.

    Article  PubMed  Google Scholar 

  11. Kavolius JP, Mastorakos DP, Pavlovich C, Russo P, Burt ME, Brady MS. Resection of metastatic renal cell carcinoma. J Clin Oncol. 1998;16:2261–6.

    PubMed  CAS  Google Scholar 

  12. Kierney PC, van Heerden JA, Segura JW, Weaver AL. Surgeon's role in the management of solitary renal cell carcinoma metastases occurring subsequent to initial curative nephrectomy: an institutional review. Ann Surg Oncol. 1994;1:345–52.

    Article  PubMed  CAS  Google Scholar 

  13. • Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 2011, 117(13), 2873–82. Out of 887 patients, 125 were treated with complete surgical resection of all metastases, achieving a significant prolongation of cancer-specific survival. Especially patients with lung-only metastases had a 74 % 5-year survival. Survival advantage was suggested for multiple metastases after complete metastasectomy. It was concluded that complete metastasectomy should be considered when technically feasible in appropriate surgical candidates.

    Article  PubMed  Google Scholar 

  14. Swanson DA. Surgery for metastases of renal cell carcinoma. Scand J Surg. 2004;93(2):150–5.

    PubMed  CAS  Google Scholar 

  15. Kwak C, Park YH, Jeong CW, Lee SE, Ku JH. Metastasectomy without systemic therapy in metastatic renal cell carcinoma: comparison with conservative treatment. Urol Int. 2007;79:145–51.

    Article  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. Hofmann HS, Neef H, Krohe K, Andreev P, Silber RE. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol. 2005;48:77–81.

    Article  PubMed  Google Scholar 

  18. Lin PP, Mirza AN, Lewis VO, Cannon CP, Tu SM, Tannir NM, Yasko AW. Patient survival after surgery for osseous metastases from renal cell carcinoma. J Bone Joint Surg Am. 2007;89:1794–801.

    Article  PubMed  Google Scholar 

  19. Kollender Y, Bickels J, Price WM, Kellar KL, Chen J, Merimsky O, Meller I, Malawer MM. Metastatic renal cell carcinoma of bone: indications and technique of surgical intervention. J Urol. 2000;164:1505–8.

    Article  PubMed  CAS  Google Scholar 

  20. Szendroi A, Dinya E, Kardos M, Szász AM, Németh Z, Ats K, Kiss J, Antal I, Romics I, Szendroi M. Prognostic factors and survival of renal clear cell carcinoma patients with bone metastases. Pathol Oncol Res. 2010;16:29–38.

    Article  PubMed  CAS  Google Scholar 

  21. • Ruys AT, Tanis PJ, Iris ND, van Duijvendijk P, Verhoef C, Porte RJ, van Gulik TM. Surgical treatment of renal cell cancer liver metastases: a population-based study. Ann Surg Oncol. 2011;18:1932–8. In a nationwide study, a favorable 5-year survival rate of 43 % was observed after surgery of RCC liver metastases. They had no operative mortality, The study indicates that selected patients with RCCLM can benefit from surgical treatment of RCC liver metastases.

    Article  PubMed  Google Scholar 

  22. Staehler MD, Kruse J, Haseke N, Stadler T, Roosen A, Karl A, Stief CG, Jauch KW, Bruns CJ. Liver resection for metastatic disease prolongs survival in renal cell carcinoma: 12-year results from a retrospective comparative analysis. World J Urol. 2010;28:543–7.

    Article  PubMed  Google Scholar 

  23. Ballarin R, Spaggiari M, Cautero N, De Ruvo N, Montalti R, Longo C, Pecchi A, Giacobazzi P, De Marco G, D'Amico G, Gerunda GE, Di Benedetto F. Pancreatic metastases from renal cell carcinoma: the state of the art. World J Gastroenterol. 2011;17:4747–56.

    Article  PubMed  Google Scholar 

  24. Sohn TA, Yeo CJ, Cameron JL, Nakeeb A, Lillemoe KD. Renal cell carcinoma metastatic to the pancreas: results of surgical management. J Gastrointest Surg. 2001;5(4):346–51.

    Article  PubMed  CAS  Google Scholar 

  25. Ghavamian R, Klein KA, Stephens DH, Welch TJ, LeRoy AJ, Richardson RL, Burch PA, Zincke H. Renal cell carcinoma metastatic to the pancreas: clinical and radiological features. Mayo Clin Proc. 2000;75(6):581–5.

    Article  PubMed  CAS  Google Scholar 

  26. Reddy S, Wolfgang CL. The role of surgery in the management of isolated metastases to the pancreas. Lancet Oncol. 2009;10:287–93.

    Article  PubMed  Google Scholar 

  27. Alamdari FI, Ljungberg B. Adrenal metastasis in renal cell carcinoma: a recommendation for adjustment of the TNM staging system. Scand J Urol Nephrol. 2005;39(4):277–82.

    Article  PubMed  Google Scholar 

  28. Muth A, Persson F, Jansson S, Johanson V, Ahlman H, Wängberg B. Prognostic factors for survival after surgery for adrenal metastasis. Eur J Surg Oncol. 2010;36(7):699–704.

    Article  PubMed  CAS  Google Scholar 

  29. Antonelli A, Cozzoli A, Simeone C, et al. Surgical treatment of adrenal metastasis from renal cell carcinoma: a single-centre experience of 45 patients. BJU Int. 2006;97:505–8.

    Article  PubMed  Google Scholar 

  30. Kim SH, Brennan MF, Russo P, Burt ME, Coit DG. The role of surgery in the treatment of clinically isolated adrenal metastasis. Cancer. 1998;82:389–94.

    Article  PubMed  CAS  Google Scholar 

  31. Nieder C, Spanne O, Nordøy T, Dalhaug A. Treatment of brain metastases from renal cell cancer. Urol Oncol. 2011;29:405–10.

    Article  PubMed  Google Scholar 

  32. Muacevic A, Kreth FW, Horstmann GA, Schmid-Elsaesser R, Wowra B, Steiger HJ, Reulen HJ. Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. J Neurosurg. 1999;91:35–43.

    Article  PubMed  CAS  Google Scholar 

  33. Hassaneen W, Suki D, Salaskar AL, Wildrick DM, Lang FF, Fuller GN, Sawaya R. Surgical management of lateral-ventricle metastases: report of 29 cases in a single-institution experience. J Neurosurg. 2010;112:1046–55.

    Article  PubMed  Google Scholar 

  34. Shuto T, Matsunaga S, Suenaga J, Inomori S, Fujino H. Treatment strategy for metastatic brain tumors from renal cell carcinoma: selection of gamma knife surgery or craniotomy for control of growth and peritumoral edema. J Neurooncol. 2010;98:169–75.

    Article  PubMed  Google Scholar 

  35. Cochran DC, Chan MD, Aklilu M, Lovato JF, Alphonse NK, Bourland JD, Urbanic JJ, McMullen KP, Shaw EG, Tatter SB, Ellis TL. The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with Gamma Knife surgery. J Neurosurg. 2012;116(5):978–83.

    Article  PubMed  CAS  Google Scholar 

  36. 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;180:873–8.

    Article  PubMed  Google Scholar 

  37. Leibovich BC, Cheville JC, Lohse CM, Zincke H, Frank I, Kwon ED, Merchan JR, Blute ML. A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. J Urol. 2005;174:1759–63.

    Article  PubMed  Google Scholar 

  38. Eggener SE, Yossepowitch O, Pettus JA, Snyder ME, Motzer RJ, Russo P. Renal cell carcinoma recurrence after nephrectomy for localized disease: predicting survival from time of recurrence. J Clin Oncol. 2006;24:3101–6.

    Article  PubMed  Google Scholar 

  39. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115–24.

    Article  PubMed  CAS  Google Scholar 

  40. • Karam JA, Rini BI, Varella L, Garcia JA, Dreicer R, Choueiri TK, Jonasch E, Matin SF, Campbell SC, Wood CG, Tannir NM. Metastasectomy after targeted therapy in patients with advanced renal cell carcinoma. J Urol. 2011;185:439–44. In this study, metastasectomy after targeted therapy was evaluated based on results from three different centres. The authors conclude that in a cohort of select patients (22) with a limited tumor burden after treatment with targeted agents, consolidative metastasectomy is feasible giving a long-term tumor-free status.

    Article  PubMed  Google Scholar 

  41. • Cowey CL, Amin C, Pruthi RS, Wallen EM, Nielsen ME, Grigson G, Watkins C, Nance KV, Crane J, Jalkut M, Moore DT, Kim WY, Godley PA, Whang YE, Fielding JR, Rathmell WK. Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma. J Clin Oncol 2010;28:1502–150. The authors show a reduction in tumor size with near 10 % and radiographic evidence of loss of intratumoral enhancement after one course of sorafenib therapy. Of the 28 patients evaluable for response, none progressed on therapy. All patients were able to proceed to surgery.

    Article  PubMed  CAS  Google Scholar 

  42. • Thomas AA, Rini BI, Stephenson AJ, Garcia JA, Fergany A, Krishnamurthi V, Novick AC, Gill IS, Klein EA, Zhou M, Campbell SC. Surgical resection of renal cell carcinoma after targeted therapy. J Urol. 2009;182:881–6. The study reports on the feasibility to perform surgical resection of possibly unresectable renal cell carcinoma after targeted therapy. In most patients there with a low morbidity, but significant complications can occur.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This review was supported by grants from The Swedish Cancer Society and Lions Cancer Research Foundation in Umeå.

Disclosure

The author wishes to disclose that he has received payment for consultancy with Bayer, Novartis, GCK, Roche, and Pfizer.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Börje Ljungberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ljungberg, B. The Role of Metastasectomy in Renal Cell Carcinoma in the Era of Targeted Therapy. Curr Urol Rep 14, 19–25 (2013). https://doi.org/10.1007/s11934-012-0293-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11934-012-0293-6

Keywords

Navigation