The neutrophil-to-lymphocyte ratio in clinical practice.
The mean NLR of the prostate cancer group was significantly higher than that of the benign prostatic hypertrophy (BPH) group (p=0.002). The mean NLR of the prostatitis group was higher than that of both the prostate cancer and BPH groups (p=0.0001). The mean NLR of the Gleason score (GS) 8-10 group was higher than that of the GS 7 and GS 5-6 groups. The authors conclude that NLR was found to vary with regard to histology of prostate biopsy and higher GS was associated with higher NLR in patients with prostate cancer.
Complete blood count is a inexpensive, comparatively routine, and practical laboratory test that gives us important information about the patient's formed blood contents. Routine peripheral blood counts may be useful in diagnosis and prognosis of many disorders, including prostatic diseases. (2-12)
NLR is measured by dividing the number of neutrophils by the number of lymphocytes. NLR may be an indicator of systemic inflammation, as neutrophils and lymphocytes are thought to be significant in tumour immunology and inflammation. Inflammation plays a significant role in the proliferation, angiogenesis, and metastasis of cancer cells and is important in the development and progression of the disease. (2,3) Even when white blood cell count is in normal range, NLR has been demonstrated to play a predictive role in the prognosis of chronic and acute inflammatory processes. (2-12)
A recent meta-analysis study concludes that a high NLR is an independent factor associated with poorer overall survival in many solid tumours (colorectal, hepatocellular, gastroesophageal, ovarian, and pancreatic carcinoma). This marker may be associated with renal or hepatic dysfunction, diabetes mellitus, abnormal thyroid function, hypertension, metabolic syndrom, hematological malignancies, known malignancy, preceding history of local or systemic infection, inflammatory diseases, and any use of medication connected to inflammatory status of patients. (9-12) The authors should have mentioned these factors.
In conclusion, we strongly believe the findings obtained from the current study will lead to further studies examining the evaluation of NLR prior to prostate biopsy to predict biopsy histology.
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Competing interests: The authors declare no competing financial or personal interests.
(1.) Gokce MI, Hamidi N, Suer E, et al. Evaluation of neutrophil-tolymphocyte ratio prior to prostate biopsy to predict biopsy histology: Results of 1836 patients. Can Urol Assoc J 2015;9:E761-5. http://dx.doi.org/10.5489/cuaj.3091
(2.) Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl LekListy 2001;102:5-14.
(3.) Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99. http://dx.doi.org/10.1016/j. cell.2010.01.025
(4.) Ozcan C, Telli O, Ozturk E, et al. The prognostic significance of preoperative leukocytosis and neutrophil-to-lymphocyte ratio in patients who underwent radical cystectomy for bladder cancer. Can Urol Assoc J 2015;9:E789-94. http://dx.doi.org/10.5489/ cuaj.3061
(5.) Maeda Y, Kawahara T, Kumano Y, et al. The neutrophil-to-lymphocyte ratio before repeat prostate needle biopsy for predicting prostate cancer. Urol Int 2015 Dec 16. [Epub ahead of print]. http://dx.doi.org/10.1 159/000442895
(6.) Kaynar M, Yildirim ME, Badem H, et al. Bladder cancer invasion predictability based on preoperative neutrophil--lymphocyte ratio. Tumour Biol 2014;35:6601-5. http://dx.doi.org/10.1007/ s13277-014-1889-x
(7.) Demirer Z, Uslu AU. More work needed in examining the relationship between mean platelet volume and inflammation in varicocele pathophysiology. Can UrolAssoe J 2015;9:E639. http://dx.doi. org/10.5489/cuaj.3114
(8.) Templeton AJ, McNamara MG, Seruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumours: A systematic review and meta-analysis. J Natl Caneer Inst 2014;106:dju124. http://dx.doi.org/10.1093/jnci/dju124
(9.) Balta S, Demirer Z, Aparci M, et al. The relation between lymphocyte-monocyte ratio and renal cell carcinoma. Urol Oneol 2015;33:421.
(10.) Demirer Z, Uslu AU. Predictive value of neutrophil-lymphocyte ratio in non-muscle-invasive bladder cancer. Urol Oneol 2016;34:1-2. http://dx.doi.org/10.1016/j.urolonc.2015.09.006
(11.) Balta S, Demirer Z, Aparci M, et al. The lymphocyte-monocyte ratio in clinical practice. J Clin Pathol 2016;69:88-9. http:// dx.doi.org/10.1136/jclinpath-2015-203233
(12.) Demirer Z, Uslu AU, Balta S. Letter to the editor: Predictive value of the neutrophil-lymphocyte ratio and mean platelet volume in testicular torsion. Korean J Urol 2015;56:601-2.
Correspondence: Dr. Zafer Demirer, Eskisehir Military Hospital, Department of Urology, Eskisehir, Turkey; firstname.lastname@example.org
Ali Guragag, MD;  Zafer Demirer, MD 
 Tatvan Military Hospital, Department of Urology, Bitlis, Turkey;  Eskisehir Military Hospital, Department of Urology, Eskisehir, Turkey
Author reply: The neutrophil-tolymphocyte ratio in clinical practice
We would like to thank our colleagues for their precise comments on our article. (1) Neutrophil-to-lymphocyte ratio (NLR) is a valuable tool for evaluation of inflammation and is obtained from an inexpensive and widely attainable laboratory test--complete blood count. Currently, there are valuable tests for prediction of prostate cancer, particularly high-grade cases. These tests include: PCA3; prostate health index (PHI) multibiomarker test, which combines free and total prostate-specific antigen (PSA) with [-2]proPSA; and four kallikrein protein biomarkers (total PSA, free PSA, intact PSA, and human kallikrein-related peptidase 2), named as 4K score. (2-4) However, these tests are expensive and not yet available worldwide. Therefore, tests that are widely available, like NLR, are especially important for use in developing countries.
Distinct phases of carcinogenesis and cancer growth cause different immune system responses. (5) Initially, association of NLR and prostate cancer was shown in metastatic cases, that is, higher NLR indicated more aggressive disease and poor response to treatment. (6) Recently, further studies investigating the role of NLR in the pre-biopsy setting were published. (1,7) In these studies, higher NLR values were found to be associated with higher rates of prostate cancer. There is also one study focusing on and early-stage and low-risk prostate cancer. In this study, Kwon et al found that lymphocyte count was associated with Gleason score upgrading and neutrophil count was associated with biochemical failure; NLR was not found to have association with any of the study endpoints. (8)
Our group also investigated the results of low-risk cases in which the patients underwent radical prostatectomy. We found that NLR was associated with higher rates of Gleason score upgrading and high-grade prostate cancer cases, but not with disease upstaging (data not yet published).
Although the results from the early-stage prostate cancer cases are conflicting, there is good proof of alterations in the immune system in the development and progression of prostate cancer. However, as it was mentioned in the comment to our study, levels of immune cells in the peripheral blood are prone to change in many circumstances. (9) Due to the retrospective nature of our study, we could not retrieve data on the conditions that might have affected levels of immune cells. On the other hand, such data, although valuable, still does not clarify the changes in immune system and immune response to development and progression of prostate cancer cells. A study with immunohistochemical examination of the prostate tissue from biopsy or radical prostatectomy specimens would better identify the changes in the prostatic tissue level.
Competing interests: The authors declare no competing financial or personal interests.
(1.) Gokce MI, Hamidi N, Suer E, et al. Evaluation of neutrophil-tolymphocyte ratio prior to prostate biopsy to predict biopsy histology: Results of 1836 patients. Can UrolAssoe J 2015;9:E761-5. http://dx.doi.org/10.5489/cuaj.3091
(2.) Cary KC, Cooperberg MR. Biomarkers in prostate cancer surveillance and screening: Past, present, and future. Ther Adv Urol 2013;5:318-29. http://dx.doi.org/10.1 177/1756287213495915
(3.) Catalona WJ, Partin AW, Sanda MG, et al. A multicenterstudy of [-2]pro-prostate-specific antigen combined with prostate-specific antigen and free prostate-specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate-specific antigen range. J Urol 2011;185:1 650-5. http://dx.doi.org/10.1016/j. juro.2010.12.032
(4.) Lilja H, Ulmert D, Vickers AJ. Prostate-specific antigen and prostate cancer: Prediction, detection, and monitoring. Nat Rev Caneer 2008;8:268-78. http://dx.doi.org/10.1038/nrc2351
(5.) Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology 2007;121:1-14. http://dx.doi.org/10.1111/j.1365-2567.2007.02587.x
(6.) van Soest RJ, Templeton AJ, Vera-Badillo FE, et al. Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: Data from two randomized phase 3 trials. Ann Oneol 2015; 26:743-9. http://dx.doi.org/10.1093/annonc/mdu569
(7.) Kawahara T, Fukui S, Sakamaki K, et al. Neutrophil-to-lymphocyte ratio predicts prostatic carcinoma in men undergoing needle biopsy. Oneotarget 2015;6:32169-76.
(8.) Kwon YS, Han CS, Yu JW, et al. Neutrophil and lymphocyte counts as clinical markers for stratifying low-risk prostate cancer. Clin Genitourin Caneer2016;14:el-8. ht1p://dx.doi.org/10.1016/j. clgc.2015.07.018
(9.) Balta S, Demirer Z, Aparci M, et al. The lymphocyte-monocyte ratio in clinical practice. J ClinPathol 2016;69:88-9. http://dx.doi. org/10.1136/jclinpath-2015-203233
Correspondence: Dr. Mehmet Gokce, Department of Urology, Ankara University School of Medicine, Ankara, Turkey; email@example.com
Mehmet Ilker Gokce, MD;  Nurullah Hamidi, MD;  Evren Suer, MD;  Semih Tangal, MD;  Adil Huseynov, MD;  Arif Ibis, MD 
 Department of Urology, Ankara University School of Medicine, Ankara, Turkey; department of Urology, Ufuk University School of Medicine, Ankara, Turkey
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|Title Annotation:||CUAJ LETTERS|
|Author:||Guragac, Ali; Demirer, Zafer|
|Publication:||Canadian Urological Association Journal (CUAJ)|
|Article Type:||Letter to the editor|
|Date:||Mar 1, 2016|
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