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Comprehensive analysis and validation of contemporary survival prognosticators in Korean patients with metastatic renal cell carcinoma treated with targeted therapy: prognostic impact of pretreatment neutrophil-to-lymphocyte ratio

  • Urology - Original Paper
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Abstract

Purpose

In line with the era of targeted therapy (TT), an increasing number of prognosticators are becoming available for patients with metastatic renal cell carcinoma (mRCC). Here, potential prognosticators of cancer-specific survival (CSS) were identified based on the contemporary literature and were comprehensively validated in an independent cohort of patients treated for mRCC.

Methods

Data were collected from 478 patients treated with TT for mRCC between January 1999 and July 2013 at a single institution. The analysis included 25 clinicopathological covariates that included both traditional and contemporary prognosticators. Multivariate Cox regression models were used to quantify the effect of covariates on CSS.

Results

Median survival from the initial diagnosis of metastasis was 24.5 (IQR, 11.5–55.7) months. There were 303 (63.4 %) cancer-specific deaths, yielding a 2-year CSS rate of 62.5 %. Low Karnofsky performance status (KPS), hypercalcemia, neutrophil-to-lymphocyte ratio (NLR), the number of metastatic sites (≥2), and the presence of brain metastases were independent adverse prognosticators of CSS. The C-index of the model was 0.78. Patients with at least one adverse prognosticator demonstrated lower 2-year CSS rates compared to those with no prognosticators (53.9 vs. 70.6 %; log rank p < 0.001).

Conclusions

Together with traditional prognosticators such as KPS, hypercalcemia, and the number and location of metastases, the NLR was an independent predictor of CSS in patients with mRCC treated with TT. Our findings could be useful for guiding clinical decision making including stratification of patients for TT and inclusion in clinical trials.

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References

  1. Chawla SN, Crispen PL, Hanlon AL, Greenberg RE, Chen DY, Uzzo RG (2006) The natural history of observed enhancing renal masses: meta-analysis and review of the world literature. J Urol 175:425–431

    Article  PubMed  Google Scholar 

  2. Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335:865–875

    Article  CAS  PubMed  Google Scholar 

  3. Margulis V, Shariat SF, Rapoport Y, Rink M, Sjoberg DD, Tannir NM et al (2013) Development of accurate models for individualized prediction of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma. Eur Urol 63:947–952

    Article  CAS  PubMed  Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. Heng DY, **e 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

    Article  CAS  PubMed  Google Scholar 

  6. Cetin B, Berk V, Kaplan MA, Afsar B, Tufan G, Ozkan M et al (2013) Is the pretreatment neutrophil to lymphocyte ratio an important prognostic parameter in patients with metastatic renal cell carcinoma? Clin Genitourin Cancer 11:141–148

    Article  PubMed  Google Scholar 

  7. Grunwald V, McKay RR, Krajewski KM, Kalanovic D, Lin X, Perkins JJ et al (2015) Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol 67:952–958

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kroeger N, Pantuck AJ, Wells JC, Lawrence N, Broom R, Kim JJ et al (2015) Characterizing the impact of lymph node metastases on the survival outcome for metastatic renal cell carcinoma patients treated with targeted therapies. Eur Urol 68:506–515

    Article  PubMed  Google Scholar 

  9. Tilki D, Hu B, Nguyen HG, Dall’Era MA, Bertini R, Carballido JA et al (2015) Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy. J Urol 193:436–442

    Article  PubMed  Google Scholar 

  10. Isbarn H, Karakiewicz PI (2009) Predicting cancer-control outcomes in patients with renal cell carcinoma. Curr Opin Urol 19:247–257

    Article  PubMed  Google Scholar 

  11. Leibovich BC, Cheville JC, Lohse CM, Zincke H, Frank I, Kwon ED et al (2005) A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. J Urol 174:1759–1763

    Article  PubMed  Google Scholar 

  12. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X et al (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:419–425

    Article  PubMed  Google Scholar 

  13. McKay RR, Kroeger N, **e W, Lee JL, Knox JJ, Bjarnason GA et al (2014) Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. Eur Urol 65:577–584

    Article  PubMed  Google Scholar 

  14. Han KR, Pantuck AJ, Bui MH, Shvarts O, Freitas DG, Zisman A et al (2003) Number of metastatic sites rather than location dictates overall survival of patients with node-negative metastatic renal cell carcinoma. Urology 61:314–319

    Article  PubMed  Google Scholar 

  15. Procopio G, Testa I, Verzoni E, Iacovelli R, Grassi P, Galli G et al (2015) Time from nephrectomy as a prognostic factor in metastatic renal cell carcinoma patients receiving targeted therapies: overall results from a large cohort of patients. Oncology 88:133–138

    Article  CAS  PubMed  Google Scholar 

  16. Kim HL, Belldegrun AS, Freitas DG, Bui MH, Han KR, Dorey FJ et al (2003) Paraneoplastic signs and symptoms of renal cell carcinoma: implications for prognosis. J Urol 170:1742–1746

    Article  PubMed  Google Scholar 

  17. Negrier S, Escudier B, Gomez F, Douillard JY, Ravaud A, Chevreau C et al (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol 13:1460–1468

    Article  CAS  PubMed  Google Scholar 

  18. 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

    Article  CAS  PubMed  Google Scholar 

  19. Wronski M, Maor MH, Davis BJ, Sawaya R, Levin VA (1997) External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center. Int J Radiat Oncol Biol Phys 37:753–759

    Article  CAS  PubMed  Google Scholar 

  20. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  PubMed  Google Scholar 

  21. Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P et al (2005) Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23:832–841

    Article  PubMed  Google Scholar 

  22. Choueiri TK, Garcia JA, Elson P, Khasawneh M, Usman S, Golshayan AR et al (2007) Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer 110:543–550

    Article  CAS  PubMed  Google Scholar 

  23. Motzer RJ, Bukowski RM, Figlin RA, Hutson TE, Michaelson MD, Kim ST et al (2008) Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma. Cancer 113:1552–1558

    Article  CAS  PubMed  Google Scholar 

  24. Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD (2003) Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 98:342–349

    Article  PubMed  Google Scholar 

  25. 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

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Urological Science Institute, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul, 135-720, Republic of Korea

    Kyo Chul Koo, Kwang Suk Lee, Kang Su Cho, Koon Ho Rha, Sung Joon Hong & Byung Ha Chung

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  1. Kyo Chul Koo
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  2. Kwang Suk Lee
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  3. Kang Su Cho
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Correspondence to Byung Ha Chung.

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All of the authors declare that they have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was not required for the purposes of this study as it was based upon retrospective anonymous patient data and did not involve patient intervention or the use of human tissue samples.

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Koo, K.C., Lee, K.S., Cho, K.S. et al. Comprehensive analysis and validation of contemporary survival prognosticators in Korean patients with metastatic renal cell carcinoma treated with targeted therapy: prognostic impact of pretreatment neutrophil-to-lymphocyte ratio. Int Urol Nephrol 48, 985–992 (2016). https://doi.org/10.1007/s11255-016-1252-9

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  • DOI: https://doi.org/10.1007/s11255-016-1252-9

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