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Radiological Response and Neutrophil-to-Lymphocyte Ratio as Predictive Factors for Progression-Free and Overall Survival in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib

  • Jakub KucharzEmail author
  • Paulina Dumnicka
  • Agnieszka Giza
  • Urszula Demkow
  • Beata Kusnierz–Cabala
  • Tomasz Demkow
  • Pawel Wiechno
Part of the Advances in Experimental Medicine and Biology book series


Renal cell carcinoma (RCC) represents 2–3% of all malignancies. Most RCC-related deaths are caused by metastases of the disease. Studies suggest that inflammation-related parameters are of prognostic significance in metastatic renal cell carcinoma (mRCC) patients. Neutrophilia and thrombocytosis are markers of systemic inflammation that accompanies cancer, while lymphopenia is related to dysfunctions of the immune system. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) thus seem particularly interesting from a clinical perspective. The goal of this study was to determine if the response to therapy, consisting of reductions in radiologically assessed tumor burden and in inflammation-related parameters after 12 weeks of treatment with sunitinib, has a predictive value for outcome. One hundred thirty-one mRCC patients treated with the first-line sunitinib were evaluated. Inflammation-related parameters and radiologic response were correlated with treatment outcomes, progression-free, and overall survival. We found that the longest median progression-free survival of 37 months (Q1; Q3–15; not reached) and overall survival of 40 months (Q1; Q3–26; not reached) were achieved by patients who had either partial or complete response according to RECIST 1.1 and NLR lower than 1.64. In conclusion, the study confirmed that both objective response and lower grade of inflammation during treatment are predictive of better outcomes in mRCC patients treated with sunitinib.


Cancer Metastases Neutrophil-to-lymphocyte ratio Radiological response Renal cell carcinoma Sunitinib Survival 


Conflicts of Interest

JK has received research grant from Novartis and travel grants and speakers’ honoraria from Pfizer, Bayer, Novartis, BMS, and IPSEN. PW has received speakers’ honoraria and travel grants from Pfizer, Bayer, Novartis, and IPSEN. The other authors declare no conflicts of interest in relation to this article.

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. The study was approved by the Bioethics Committee of the Maria Sklodowska-Curie Memorial Cancer Center and the Institute of Oncology (permission 38/2018).

Informed Consent

For this retrospective type of study, formal consent from individual patients was not required.


  1. Athar U, Gentile TC (2008) Treatment options for metastatic renal cell carcinoma: a review. Can J Urol 15(2):3954–3966Google Scholar
  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2008) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424Google Scholar
  3. Choueiri TK, Hessel C, Halabi S, Sanford B, Michaelson MD, Hahn O, Walsh M, Olencki T, Picus J, Small EJ, Dakhil S, Feldman DR, Mangeshkar M, Scheffold C, George D, Morris MJ (2018) Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): progression–free survival by independent review and overall survival update. Eur J Cancer 94:115–125Google Scholar
  4. CTCAE (2010) version 4.03. U.S. Department of Health and Human Services NIH, National Cancer Institute. Common terminology criteria for adverse events.–06–14_QuickReference_5x7.pdf. Accessed on 23 Feb 2019
  5. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247Google Scholar
  6. European Network of Cancer Registries: EUROCIM version 4.0. 2001: Lyon, FranceGoogle Scholar
  7. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899Google Scholar
  8. Gu L, Li H, Chen L, Ma X, Li X, Gao Y, Zhang Y, Xie Y, Zhang X (2016) Prognostic role of lymphocyte to monocyte ratio for patients with cancer: evidence from a systematic review and meta–analysis. Oncotarget 7:31926–31942Google Scholar
  9. 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(3):193–205Google Scholar
  10. Han X, Ruan J, Zhang W, Zhou D, Xu D, Pei Q, Ouyang M, Zuo M (2017) Prognostic implication of leucocyte subpopulations in diffuse large B–cell lymphoma. Oncotarget 8(29):47790–47800Google Scholar
  11. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S, Venner P, Knox JJ, Chi KN, Kollmannsberger C, McDermott DF, Oh WK, Atkins MB, Bukowski RM, Rini BI, Choueiri TK (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(34):5794–5799Google Scholar
  12. Keizman D, Ish–Shalom M, Huang P, Eisenberger MA, Pili R, Hammers H, Carducci MA (2012) The association of pre–treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer 48(2):202–208Google Scholar
  13. Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN (2009) Blood neutrophil–to–lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol 16(3):614–622Google Scholar
  14. Kowalczyk DW, Przybylski GK, Lisiecka D, Słomski R, Nowak JS (2006) Gamma/delta tumor infiltrating lymphocytes selectively infiltrate human renal cell carcinomas. Centr. Eur J Immunol 31(3–4):75–83Google Scholar
  15. Lalani AA, Xie W, Martini DJ, Steinharter JA, Norton CK, Krajewski KM, Duquette A, Bossé D, Bellmunt J, Van Allen EM, McGregor BA, Creighton CJ, Harshman LC, Choueiri TK (2018) Change in neutrophil–to–lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. J Immunother Cancer 6(1):5Google Scholar
  16. Lee S, Oh SY, Kim SH, Lee JH, Kim MC, Kim KH, Kim HJ (2013) Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy. BMC Cancer 13:350Google Scholar
  17. Leibovich BC, Blute ML, Cheville JC, Lohse CM, Frank I, Kwon ED, Weaver AL, Parker AS, Zincke H (2003) Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer 97(7):1663–1671Google Scholar
  18. Ljungberg B, Grankvist K, Rasmuson T (1997) Serum interleukin–6 in relation to acute–phase reactants and survival in patients with renal cell carcinoma. Eur J Cancer 33:1794–1798Google Scholar
  19. Molina AM, Lin X, Korytowsky B, Matczak E, Lechuga MJ, Wiltshire R, Motzer RJ (2014) Sunitinib objective response in metastatic renal cell carcinoma: analysis of 1059 patients treated on clinical trials. Eur J Cancer 50(2):351–358Google Scholar
  20. 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(8):2530–2540Google Scholar
  21. 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 (2007) Sunitinib versus interferon alfa in metastatic renal–cell carcinoma. N Engl J Med 356(2):115–124Google Scholar
  22. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia–del–Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27(22):3584–3590Google Scholar
  23. Motzer RJ, Escudier B, Bukowski R, Rini BI, Hutson TE, Barrios CH, Lin X, Fly K, Matczak E, Gore ME (2013) Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma. Br J Cancer 108(12):2470–2477Google Scholar
  24. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B, CheckMate 214 Investigators (2018) Nivolumab plus Ipilimumab versus Sunitinib in advanced renal–cell carcinoma. N Engl J Med 378(14):1277–1290Google Scholar
  25. Pastewka K, Zawadzki M, Rudziński M (2010) Antiangiogenic treatment in renal cell carcinoma. Cent Eur J Immunol 35(4):249–251Google Scholar
  26. Seidel C, Busch J, Weikert S, Steffens S, Bokemeyer C, Grünwald V (2013) Tumour shrinkage measured with first treatment evaluation under VEGF–targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC). Br J Cancer 109(12):2998–3004Google Scholar
  27. Tannir NM, Figlin RA, Gore ME, Michaelson MD, Motzer RJ, Porta C, Rini BI, Hoang C, Lin X, Escudier B (2017) Long–term response to sunitinib treatment in metastatic renal cell carcinoma: a pooled analysis of clinical trials. Clin Genitourin Cancer. Scholar
  28. Tatokoro M, Saito K, Iimura Y, Fujii Y, Kawakami S, Kihara K (2008) Prognostic impact of postoperative C–reactive protein level in patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy. J Urol 180(2):515–519Google Scholar
  29. Templeton AJ, Knox JJ, Lin X, Simantov R, Xie W, Lawrence N, Broom R, Fay AP, Rini B, Donskov F, Bjarnason GA, Smoragiewicz M, Kollmannsberger C, Kanesvaran R, Alimohamed N, Hermanns T, Wells JC, Amir E, Choueiri TK, Heng DY (2016) Change in neutrophil–to–lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy. Eur Urol 70(2):358–364Google Scholar
  30. Uribe–Querol E, Rosales C (2015) Neutrophils in cancer: two sides of the same coin. J Immunol Res 2015:983698Google Scholar
  31. Wojtukiewicz MZ, Sierko E, Hempel D, Tucker SC, Honn KV (2017) Platelets and cancer angiogenesis nexus. Cancer Metastasis Rev 36(2):249–262Google Scholar
  32. Wu Y, Li C, Zhao J, Yang L, Liu F, Zheng H, Wang Z, Xu Y (2016) Neutrophil–to–lymphocyte and platelet–to–lymphocyte ratios predict chemotherapy outcomes and prognosis in patients with colorectal cancer and synchronous liver metastasis. World J Surg Oncol 14(1):289Google Scholar
  33. Xiao WK, Chen D, Li SQ, Fu SJ, Peng BG, Liang LJ (2014) Prognostic significance of neutrophil–lymphocyte ratio in hepatocellular carcinoma: a meta–analysis. BMC Cancer 14:117Google Scholar
  34. Zhang GM, Zhu Y, Gu WJ, Zhang HL, Shi GH, Ye DW (2016) Pretreatment neutrophil–to–lymphocyte ratio predicts prognosis in patients with metastatic renal cell carcinoma receiving targeted therapy. Int J Clin Oncol 1(2):373–378Google Scholar
  35. Zhang Y, Lu j DY, Feng C, Li W, Chen M (2018) Prognostic value of neutrophil–to–lymphocyte ratio and platelet–to–lymphocyte ratio in gastric cancer. Medicine 97:1–5Google Scholar
  36. Zhao P, Zang L, Zhang X, Chen Y, Yue Z, Yang H, Zhao H, Yu Y, Wang Y, Zhao Z, Zhang Y, Wang X (2018) Novel prognostic scoring system for diffuse large B–cell lymphoma. Oncol Lett 15(4):5325–5332Google Scholar
  37. Zhou X, Du Y, Huang Z, Xu J, Qiu T, Wang J, Wang T, Zhu W, Liu P (2014) Prognostic value of PLR in various cancers: a meta–analysis. PLoS One 9(6):e101119Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Jakub Kucharz
    • 1
    Email author
  • Paulina Dumnicka
    • 2
  • Agnieszka Giza
    • 3
  • Urszula Demkow
    • 4
  • Beata Kusnierz–Cabala
    • 5
  • Tomasz Demkow
    • 1
  • Pawel Wiechno
    • 1
  1. 1.Department of UrooncologyMaria Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  2. 2.Department of Medical DiagnosticsJagiellonian University Medical CollegeCracowPoland
  3. 3.Department of HematologyJagiellonian University Medical CollegeCracowPoland
  4. 4.Department of Laboratory Diagnostics and Clinical Immunology of Developmental AgeWarsaw Medical UniversityWarsawPoland
  5. 5.Department of Diagnostics, Chair of Clinical BiochemistryJagiellonian University Medical CollegeCracowPoland

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