Skip to main content
Top
Published in: World Journal of Urology 11/2015

01-11-2015 | Original Article

Validation of the neutrophil-to-lymphocyte ratio as a prognostic factor in a cohort of European prostate cancer patients

Authors: Tanja Langsenlehner, Eva-Maria Thurner, Sabine Krenn-Pilko, Uwe Langsenlehner, Tatjana Stojakovic, Armin Gerger, Martin Pichler

Published in: World Journal of Urology | Issue 11/2015

Login to get access

Abstract

Purpose

Recent studies have expanded the concept that the systemic inflammatory response has an important role in the progression of several solid tumors. The neutrophil-to-lymphocyte ratio (NLR), an easily determinable marker of systemic inflammation, has been associated with clinical outcome in various cancer entities. In the present study, we validated the prognostic relevance of an elevated NLR in a cohort of European prostate cancer patients.

Methods

Data from 415 consecutive prostate cancer patients treated with 3D conformal radiotherapy at a single tertiary academic center from 1999 to 2007 were included in this retrospective study. Clinical progression-free survival (PFS), distant metastases-free survival (DMFS), and overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the prognostic relevance, univariate and multivariate Cox regression models were performed for each end point.

Results

Based on previously published studies, an NLR ≥ 5 was selected as cutoff value for external validation. Multivariate analysis identified an increased NLR as an independent prognostic factor for clinical PFS [hazard ratio (HR) 3.09, 95 % CI 1.64–5.82, p < 0.001], DMFS (HR 3.51, 95 % CI 1.80–6.85, p < 0.001), and OS (HR 2.16, 95 % CI 1.17–3.99, p = 0.013).

Conclusion

The NLR seems to represent an independent prognostic marker and should be considered for future individual risk assessment in patients with prostate cancer.
Literature
1.
go back to reference Castelli T, Cimino S, Magno C, Morgia G (2010) Molecular markers for prostatic cancer. Front Biosci (Elite Ed) 2:641–656CrossRef Castelli T, Cimino S, Magno C, Morgia G (2010) Molecular markers for prostatic cancer. Front Biosci (Elite Ed) 2:641–656CrossRef
2.
go back to reference Huang HC, Zheng S, VanBuren V, Zhao Z (2010) Discovering disease-specific biomarker genes for cancer diagnosis and prognosis. Technol Cancer Res Treat 9:219–230CrossRefPubMed Huang HC, Zheng S, VanBuren V, Zhao Z (2010) Discovering disease-specific biomarker genes for cancer diagnosis and prognosis. Technol Cancer Res Treat 9:219–230CrossRefPubMed
3.
6.
go back to reference Szkandera J, Gerger A, Liegl-Atzwanger B, Absenger G, Stotz M, Samonigg H, Maurer-Ertl W, Stojakovic T, Ploner F, Leithner A, Pichler M (2013) Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients. Br J Cancer. doi:10.1038/bjc.2013.595 Szkandera J, Gerger A, Liegl-Atzwanger B, Absenger G, Stotz M, Samonigg H, Maurer-Ertl W, Stojakovic T, Ploner F, Leithner A, Pichler M (2013) Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients. Br J Cancer. doi:10.​1038/​bjc.​2013.​595
7.
8.
go back to reference Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O'Reilly DS, Foulis AK, Horgan PG, McMillan DC (2011) A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer 47:2633–2641. doi:10.1016/j.ejca.2011.03.028 CrossRefPubMed Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O'Reilly DS, Foulis AK, Horgan PG, McMillan DC (2011) A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer 47:2633–2641. doi:10.​1016/​j.​ejca.​2011.​03.​028 CrossRefPubMed
9.
go back to reference Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, Kornprat P, AlZoughbi W, Seggewies FS, Lackner C, Stojakovic T, Samonigg H, Hoefler G, Pichler M (2013) Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer 109:416–421. doi:10.1038/bjc.2013.332 PubMedCentralCrossRefPubMed Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, Kornprat P, AlZoughbi W, Seggewies FS, Lackner C, Stojakovic T, Samonigg H, Hoefler G, Pichler M (2013) Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer 109:416–421. doi:10.​1038/​bjc.​2013.​332 PubMedCentralCrossRefPubMed
10.
go back to reference Pichler M, Hutterer GC, Stoeckigt C, Chromecki TF, Stojakovic T, Golbeck S, Eberhard K, Gerger A, Mannweiler S, Pummer K, Zigeuner R (2013) Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients. Br J Cancer 108:901–907. doi:10.1038/bjc.2013.28 PubMedCentralCrossRefPubMed Pichler M, Hutterer GC, Stoeckigt C, Chromecki TF, Stojakovic T, Golbeck S, Eberhard K, Gerger A, Mannweiler S, Pummer K, Zigeuner R (2013) Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients. Br J Cancer 108:901–907. doi:10.​1038/​bjc.​2013.​28 PubMedCentralCrossRefPubMed
11.
go back to reference Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106:dju124. doi:10.1093/jnci/dju124 CrossRefPubMed Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106:dju124. doi:10.​1093/​jnci/​dju124 CrossRefPubMed
12.
go back to reference Nuhn P, Vaghasia AM, Goyal J, Zhou XC, Carducci MA, Eisenberger MA, Antonarakis ES (2013) Association of pretreatment neutrophil-to-lymphocyte ratio (NLR) and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel. BJU Int. doi:10.1111/bju.12531 Nuhn P, Vaghasia AM, Goyal J, Zhou XC, Carducci MA, Eisenberger MA, Antonarakis ES (2013) Association of pretreatment neutrophil-to-lymphocyte ratio (NLR) and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel. BJU Int. doi:10.​1111/​bju.​12531
13.
go back to reference Templeton AJ, Pezaro C, Omlin A, McNamara MG, Leibowitz-Amit R, Vera-Badillo FE, Attard G, de Bono JS, Tannock IF, Amir E (2014) Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer. doi:10.1002/cncr.28890 PubMed Templeton AJ, Pezaro C, Omlin A, McNamara MG, Leibowitz-Amit R, Vera-Badillo FE, Attard G, de Bono JS, Tannock IF, Amir E (2014) Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer. doi:10.​1002/​cncr.​28890 PubMed
14.
go back to reference Sümbül AT, Sezer A, Abalı H, Köse F, Gültepe I, Mertsoylu H, Muallaoğlu S, Ozyılkan O (2014) Neutrophil-to-lymphocyte ratio predicts PSA response, but not outcomes in patients with castration-resistant prostate cancer treated with docetaxel. Int Urol Nephrol 46:1531–1535. doi:10.1007/s11255-014-0664-7 CrossRefPubMed Sümbül AT, Sezer A, Abalı H, Köse F, Gültepe I, Mertsoylu H, Muallaoğlu S, Ozyılkan O (2014) Neutrophil-to-lymphocyte ratio predicts PSA response, but not outcomes in patients with castration-resistant prostate cancer treated with docetaxel. Int Urol Nephrol 46:1531–1535. doi:10.​1007/​s11255-014-0664-7 CrossRefPubMed
15.
go back to reference Leibowitz-Amit R, Templeton AJ, Omlin A, Pezaro C, Atenafu EG, Keizman D, Vera-Badillo F, Seah JA, Attard G, Knox JJ, Sridhar SS, Tannock IF, de Bono JS, Joshua AM (2014) Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Ann Oncol 25:657–662. doi:10.1093/annonc/mdt581 PubMedCentralCrossRefPubMed Leibowitz-Amit R, Templeton AJ, Omlin A, Pezaro C, Atenafu EG, Keizman D, Vera-Badillo F, Seah JA, Attard G, Knox JJ, Sridhar SS, Tannock IF, de Bono JS, Joshua AM (2014) Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Ann Oncol 25:657–662. doi:10.​1093/​annonc/​mdt581 PubMedCentralCrossRefPubMed
16.
go back to reference Keizman D, Gottfried M, Ish-Shalom M, Maimon N, Peer A, Neumann A, Rosenbaum E, Kovel S, Pili R, Sinibaldi V, Carducci MA, Hammers H, Eisenberger MA, Sella A (2012) Pretreatment neutrophil-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with ketoconazole: association with outcome and predictive nomogram. Oncologist 17:1508–1514. doi:10.1634/theoncologist.2012-0125 PubMedCentralCrossRefPubMed Keizman D, Gottfried M, Ish-Shalom M, Maimon N, Peer A, Neumann A, Rosenbaum E, Kovel S, Pili R, Sinibaldi V, Carducci MA, Hammers H, Eisenberger MA, Sella A (2012) Pretreatment neutrophil-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with ketoconazole: association with outcome and predictive nomogram. Oncologist 17:1508–1514. doi:10.​1634/​theoncologist.​2012-0125 PubMedCentralCrossRefPubMed
17.
go back to reference Shafique K, Proctor MJ, McMillan DC, Qureshi K, Leung H, Morrison DS (2012) Systemic inflammation and survival of patients with prostate cancer: evidence from the Glasgow Inflammation Outcome Study. Prostate Cancer Prostatic Dis 15:195–201. doi:10.1038/pcan.2011.60 CrossRefPubMed Shafique K, Proctor MJ, McMillan DC, Qureshi K, Leung H, Morrison DS (2012) Systemic inflammation and survival of patients with prostate cancer: evidence from the Glasgow Inflammation Outcome Study. Prostate Cancer Prostatic Dis 15:195–201. doi:10.​1038/​pcan.​2011.​60 CrossRefPubMed
18.
go back to reference De Larco JE, Wuertz BRK, Furcht LT (2004) The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res 10:4895–4900CrossRefPubMed De Larco JE, Wuertz BRK, Furcht LT (2004) The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res 10:4895–4900CrossRefPubMed
19.
go back to reference Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69:1553–1560PubMedCentralCrossRefPubMed Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69:1553–1560PubMedCentralCrossRefPubMed
20.
go back to reference Müller I, Munder M, Kropf P, Hänsch GM (2009) Polymorphonuclear neutrophils and T lymphocytes: Strange bedfellows or brothers in arms? Trends Immunol 30:522–530CrossRefPubMed Müller I, Munder M, Kropf P, Hänsch GM (2009) Polymorphonuclear neutrophils and T lymphocytes: Strange bedfellows or brothers in arms? Trends Immunol 30:522–530CrossRefPubMed
21.
go back to reference An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH, Jiang WQ (2010) Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers 15:516–522CrossRefPubMed An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH, Jiang WQ (2010) Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers 15:516–522CrossRefPubMed
22.
23.
go back to reference Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105:93–103PubMedCentralCrossRefPubMed Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105:93–103PubMedCentralCrossRefPubMed
24.
go back to reference Ege H, Gertz MA, Markovic SN, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Porrata LF (2008) Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma: a retrospective study. Br J Haematol 141:792–798CrossRefPubMed Ege H, Gertz MA, Markovic SN, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Porrata LF (2008) Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma: a retrospective study. Br J Haematol 141:792–798CrossRefPubMed
25.
go back to reference Leitch EF, Chakrabarti M, Crozier JE, McKee RF, Anderson JH, Horgan PG, McMillan DC (2007) Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer 97:1266–1270PubMedCentralCrossRefPubMed Leitch EF, Chakrabarti M, Crozier JE, McKee RF, Anderson JH, Horgan PG, McMillan DC (2007) Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer 97:1266–1270PubMedCentralCrossRefPubMed
26.
go back to reference Nieto Y, Nawaz S, Shpall EJ, Bearman SI, Murphy J, Jones RB (2004) Long-term analysis and prospective validation of a prognostic model for patients with high-risk primary breast cancer receiving high-dose chemotherapy. Clin Cancer Res 10:2609–2617CrossRefPubMed Nieto Y, Nawaz S, Shpall EJ, Bearman SI, Murphy J, Jones RB (2004) Long-term analysis and prospective validation of a prognostic model for patients with high-risk primary breast cancer receiving high-dose chemotherapy. Clin Cancer Res 10:2609–2617CrossRefPubMed
27.
go back to reference Sonpavde G, Pond GR, Armstrong AJ, Clarke SJ, Vardy JL, Templeton AJ, Wang SL, Paolini J, Chen I, Chow-Maneval E, Lechuga M, Smith MR, Michaelson MD (2014) Prognostic Impact of the neutrophil-to-lymphocyte ratio in men with metastatic castration-resistant prostate cancer. Clin Genitourin Cancer 12:317–324. doi:10.1016/j.clgc.2014.03.005 CrossRefPubMed Sonpavde G, Pond GR, Armstrong AJ, Clarke SJ, Vardy JL, Templeton AJ, Wang SL, Paolini J, Chen I, Chow-Maneval E, Lechuga M, Smith MR, Michaelson MD (2014) Prognostic Impact of the neutrophil-to-lymphocyte ratio in men with metastatic castration-resistant prostate cancer. Clin Genitourin Cancer 12:317–324. doi:10.​1016/​j.​clgc.​2014.​03.​005 CrossRefPubMed
Metadata
Title
Validation of the neutrophil-to-lymphocyte ratio as a prognostic factor in a cohort of European prostate cancer patients
Authors
Tanja Langsenlehner
Eva-Maria Thurner
Sabine Krenn-Pilko
Uwe Langsenlehner
Tatjana Stojakovic
Armin Gerger
Martin Pichler
Publication date
01-11-2015
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 11/2015
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-015-1494-7

Other articles of this Issue 11/2015

World Journal of Urology 11/2015 Go to the issue