Journal of Neuro-Oncology

, Volume 130, Issue 1, pp 221–228 | Cite as

Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma

  • YueJun Du
  • Sascha PahernikEmail author
  • Boris Hadaschik
  • Dogu Teber
  • Stephan Duensing
  • Dirk Jäger
  • Markus Hohenfellner
  • Carsten Grüllich
Clinical Study


Patients with brain metastasis (BM) from renal cell carcinoma (RCC) are associated with poor prognosis. Between 1990 and 2015, data of consecutive RCC patients with BM were retrospectively analyzed from a urologic oncologic database. The treatment outcome was evaluated by overall survival (OS), which was defined as interval from initial diagnosis of BM to death or last follow-up. Statistical analyses of clinical and pathological variables were performed using Cox regression and the Kaplan–Meier method. A total of 116 RCC patients with BM were included. Median time from initial diagnosis of RCC to BM was 15.8 months (95 % CI 11.6–20.0). Median OS after diagnosis of brain metastases of the whole cohort was 5.8 months (95 % CI 4.3–7.2). On multivariate Cox regression analysis, age and histology of non-clear cell RCC were associated with poorer outcome, while targeted therapy (n = 26) (OS 9.9 months, 95 % CI 3.3–16.5) and BM resection (n = 33) (OS 24.7 months, 95 % CI 4–40) were associated with better survival. Furthermore, patients who underwent both targeted therapy and BM resection (n = 5) had the best outcome with median OS of 52.4 months. In conclusion, BM from RCC is associated with a poor oncological outcome. Furthermore, age and histology of non-clear cell RCC are risk factors for poor prognosis. Patients with resectable BM may comprise a better prognostic group. Here, a better OS for resected than unresected patients was observed, which warrants BM resection. A combined modality approach of resection and targeted therapy appears to further improve the outcome of these patients while additional radiation seems to add no benefit.


Renal cell cancer Brain metastasis Targeted therapy Survival Prognosis 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.


  1. 1.
    Athar U, Gentile TC (2008) Treatment options for metastatic renal cell carcinoma: a review. Can J Urol 15:3954–3966PubMedGoogle Scholar
  2. 2.
    Brookman-May S, May M, Shariat SF, Xylinas E, Stief C, Zigeuner R, Chromecki T, Burger M, Wieland WF, Cindolo L et al (2013) Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project). Eur Urol 64:472–477CrossRefPubMedGoogle Scholar
  3. 3.
    Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P et al (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23:973–980CrossRefPubMedGoogle Scholar
  4. 4.
    Schouten LJ, Rutten J, Huveneers HA, Twijnstra A (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698–2705CrossRefPubMedGoogle Scholar
  5. 5.
    Decker DA, Decker VL, Herskovic A, Cummings GD (1984) Brain metastases in patients with renal cell carcinoma: prognosis and treatment. J Clin Oncol 2:169–173PubMedGoogle Scholar
  6. 6.
    Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, Pantuck AJ, Belldegrun AS (2008) Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival. Cancer 113:1641–1648CrossRefPubMedGoogle Scholar
  7. 7.
    Grüllich C, Vallet S, Hecht C, Duensing S, Hadaschik B, Jager D, Hohenfellner M, Pahernik S (2015) Local salvage therapy for late (≥2 years) metastatic and local relapse of renal cell cancer is a potentially curative treatment irrespective of the site of recurrence. Urol Oncol. doi:  10.1016/j.urolonc.2015.11.022 Google Scholar
  8. 8.
    Remon J, Lianes P, Martinez S (2012) Brain metastases from renal cell carcinoma. Should we change the current standard? Cancer Treat Rev 38:249–257CrossRefPubMedGoogle Scholar
  9. 9.
    Jonasch E, Gao J, Rathmell WK (2014) Renal cell carcinoma. BMJ 349:g4797CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134CrossRefPubMedGoogle Scholar
  11. 11.
    Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111CrossRefPubMedGoogle Scholar
  12. 12.
    Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281CrossRefPubMedGoogle Scholar
  13. 13.
    Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456CrossRefPubMedGoogle Scholar
  14. 14.
    Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124CrossRefPubMedGoogle Scholar
  15. 15.
    Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG et al (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378:1931–1939CrossRefPubMedGoogle Scholar
  16. 16.
    Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068CrossRefPubMedGoogle Scholar
  17. 17.
    Vallet S, Pahernik S, Hofner T, Tosev G, Hadaschik B, Duensing S, Sedlaczek O, Hohenfellner M, Jager D, Grüllich C, Renal Cancer Center at the National Center for Tumor Diseases (2015) Efficacy of targeted treatment beyond third-line therapy in metastatic kidney cancer: retrospective analysis from a large-volume cancer center. Clin Genitourin Cancer 13:e145–e152CrossRefPubMedGoogle Scholar
  18. 18.
    Gore ME, Hariharan S, Porta C, Bracarda S, Hawkins R, Bjarnason GA, Oudard S, Lee SH, Carteni G, Nieto A et al (2011) Sunitinib in metastatic renal cell carcinoma patients with brain metastases. Cancer 117:501–509CrossRefPubMedGoogle Scholar
  19. 19.
    Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J et al (2010) Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 116:1272–1280CrossRefPubMedGoogle Scholar
  20. 20.
    Kusuda Y, Miyake H, Terakawa T, Furukawa J, Muramaki M, Fujisawa M (2011) Treatment of brain metastases from renal cell carcinoma with sunitinib and radiotherapy: our experience and review of the literature. Int J Urol 18:326–329CrossRefPubMedGoogle Scholar
  21. 21.
    Lim ZD, Mahajan A, Weinberg J, Tannir NM (2013) Outcome of patients with renal cell carcinoma metastatic to the brain treated with sunitinib without local therapy. Am J Clin Oncol Cancer Clin Trials 36:258–260CrossRefGoogle Scholar
  22. 22.
    Verma J, Jonasch E, Allen P, Tannir N, Mahajan A (2011) Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. Cancer 117:4958–4965CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37: 745–751CrossRefPubMedGoogle Scholar
  24. 24.
    Bastos DA, Molina AM, Hatzoglou V, Jia X, Velasco S, Patil S, Voss MH, Feldman DR, Motzer RJ (2015) Safety and efficacy of targeted therapy for renal cell carcinoma with brain metastasis. Clin Genitourin Cancer 13:59–66CrossRefPubMedGoogle Scholar
  25. 25.
    Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Verma J, Jonasch E, Allen PK, Weinberg JS, Tannir N, Chang EL, Mahajan A (2013) The impact of tyrosine kinase inhibitors on the multimodality treatment of brain metastases from renal cell carcinoma. Am J Clin Oncol 36:620–624CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Patil S, Figlin RA, Hutson TE, Michaelson MD, Negrier S, Kim ST, Huang X, Motzer RJ (2011) Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol 22:295–300CrossRefPubMedGoogle Scholar
  28. 28.
    Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S 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 27:5794–5799CrossRefPubMedGoogle Scholar
  29. 29.
    Lin J, Jandial R, Nesbit A, Badie B, Chen MK (2015) Current and emerging treatments for brain metastases. Oncol New York 29:250–257Google Scholar
  30. 30.
    Cannady SB, Cavanaugh KA, Lee SY, Bukowski RM, Olencki TE, Stevens GH, Barnett GH, Suh JH (2004) Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study. Int J Radiat Oncol Biol Phys 58:253–258CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • YueJun Du
    • 1
    • 3
  • Sascha Pahernik
    • 1
    • 2
    Email author
  • Boris Hadaschik
    • 1
  • Dogu Teber
    • 1
  • Stephan Duensing
    • 4
  • Dirk Jäger
    • 5
  • Markus Hohenfellner
    • 1
  • Carsten Grüllich
    • 5
  1. 1.Department of UrologyHeidelberg University HospitalHeidelbergGermany
  2. 2.Department of UrologyNuremberg General Hospital, Paracelsus Medical UniversityNurembergGermany
  3. 3.Department of UrologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
  4. 4.Section of Molecular Urooncology, Department of UrologyHeidelberg University HospitalHeidelbergGermany
  5. 5.Department of Medical OncologyHeidelberg University Hospital, National Center for Tumor Diseases HeidelbergHeidelbergGermany

Personalised recommendations