Introduction: Due to variety of treatment alternatives for testicular tumours, parameters other than existing staging criteria are also needed. Most studies have revealed the correlation between cancer and inflammation. In this study, we aimed to investigate the value of preoperative inflammatory markers between early-stage testicular tumours and patients with advanced-stage, their relationship with tumour pathology and their importance in predicting stage. To calculate the differences between inflammatory markers, stage 1 tumours localized to the testis and advanced-stage tumours spread beyond the testis were classified into 2 groups according to tumour pathology. Materials and Methods: The data of 112 patients undergoing inguinal orchiectomy in between 2008 and 2018 were recorded retrospectively. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammation index (SII) were calculated by using the numbers of blood cell counts based systemic markers of inflammation. The differences between markers of inflammation were calculated by dividing tumours into 2 groups including early-stage and advanced- stage testicle tumours. Results: According to the results of preoperative inflammatory markers in predicting the stage; in the seminoma group, the difference between the median NLR (2.37 vs. 4.39, p = 0.012), LMR (3.80 vs. 2.40, p = 0.018) and SII (612 vs. 1,127, p = 0.009) of stage 1 and advanced stage were statistically significant, while in the non-seminoma group, only the difference between median PLR (99 vs. 154, p = 0.002) of stage 1 and advanced stage was statistically significant. Sensitivity and specificity of predicting advanced stage according to cut-off values of markers were 69 and 75% in NLR (3.21), 83 and 75% in LMR, and 59 and 75% in SII in the seminoma group; on the other hand, in the non-seminoma group, the sensitivity, and specificity of predicting the advanced stage of PLR cut-off (104) were 71 and 88% respectively. Conclusions: The clinical use of inflammatory biomarkers in testicular tumours may represent an important step in understanding germ cell tumours biology and in supporting staging criteria and prognostic criteria.

1.
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012.
Eur J Cancer
. 2013 Apr;49(6):1374–403.
2.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation.
Cell
. 2011 Mar;144(5):646–74.
3.
Su L, Zhang M, Zhang W, Cai C, Hong J. Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: A systematic review and meta-analysis.
Medicine (Baltimore)
. 2017 Mar;96(11):e6364.
4.
Manegold C. The causes and prognostic significance of low hemoglobin levels in tumor patients.
Strahlenther Onkol
. 1998 Dec;174 Suppl 4:17–9.
5.
Grimm T, Buchner A, Schneevoigt B, Kretschmer A, Apfelbeck M, Grabbert M, et al. Impact of preoperative hemoglobin and CRP levels on cancer-specific survival in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: results of a single-center study.
World J Urol
. 2016 May;34(5):703–8.
6.
Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis.
J Natl Cancer Inst
. 2014 May;106(6):dju124.
7.
Wang X, Su S, Guo Y. The clinical use of the platelet to lymphocyte ratio and lymphocyte to monocyte ratio as prognostic factors in renal cell carcinoma: a systematic review and meta-analysis.
Oncotarget
. 2017 Sep;8(48):84506–14.
8.
Chovanec M, De Giorgi U, Mego M. Immune-Related Concepts in Biology and Treatment of Germ-Cell Tumors.
Adv Urol
. 2018 Mar;2018:3718165.
9.
Hu B, Yang XR, Xu Y, Sun YF, Sun C, Guo W, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma.
Clin Cancer Res
. 2014 Dec;20(23):6212–22.
10.
Chovanec M, Cierna Z, Miskovska V, Machalekova K, Kalavska K, Rejlekova K, et al. Systemic immune-inflammation index is prognostic in testicular germ cell tumors with PD-L1 expressing tumor infiltrating lymphocytes.
J Clin Oncol
. 2017;35(15_suppl):e16042.
11.
Fridlender ZG, Albelda SM. Tumor-associated neutrophils: friend or foe?
Carcinogenesis
. 2012 May;33(5):949–55.
12.
el-Hag A, Clark RA. Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system.
J Immunol
. 1987 Oct;139(7):2406–13.
13.
Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis.
Br J Cancer
. 2011 Jun;105(1):93–103.
14.
Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis.
Cancer Cell
. 2011 Nov;20(5):576–90.
15.
Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor.
Cancer Cell
. 2013 Jul;24(1):130–7.
16.
Luo Y, She DL, Xiong H, Fu SJ, Yang L. Pretreatment Neutrophil to Lymphocyte Ratio as a Prognostic Predictor of Urologic Tumors: A Systematic Review and Meta-Analysis.
Medicine (Baltimore)
. 2015 Oct;94(40):e1670.
17.
Wei Y, Jiang YZ, Qian WH. Prognostic role of NLR in urinary cancers: a meta-analysis.
PLoS One
. 2014 Mar;9(3):e92079.
18.
Wang J, Liu Y, Zhang N, Li X, Xin P, Bi J, et al. Prognostic role of pretreatment platelet to lymphocyte ratio in urologic cancer.
Oncotarget
. 2017 Aug;8(41):70874–82.
19.
Li B, Zhou P, Liu Y, Wei H, Yang X, Chen T, et al. Platelet-to-lymphocyte ratio in advanced Cancer: review and meta-analysis.
Clin Chim Acta
. 2018 Aug;483:48–56.
20.
Jankovich M, Jankovichova T, Ondrus D, Breza J. Neutrophil-to-lymphocyte ratio as a predictor of preoperative tumor staging in testicular germ cell tumors.
Bratisl Lek Listy
. 2017;118(9):510–2.
21.
Bolat D, Aydoğdu Ö, Polat S, Yarımoğlu S, Bozkurt IH, Yonguç T, et al. Predictive value of preoperative neutrophil-to-lymphocyte ratio on the prognosis of germ cell testicular tumors.
Turk J Urol
. 2017 Mar;43(1):55–61.
22.
Yuksel OH, Verit A, Sahin A, Urkmez A, Uruc F. White blood cell counts and neutrophil to lymphocyte ratio in the diagnosis of testicular cancer: a simple secondary serum tumor marker.
Int Braz J Urol
. 2016 Jan-Feb;42(1):53–9.
23.
Hong X, Cui B, Wang M, Yang Z, Wang L, Xu Q. Systemic Immune-inflammation Index, Based on Platelet Counts and Neutrophil-Lymphocyte Ratio, Is Useful for Predicting Prognosis in Small Cell Lung Cancer.
Tohoku J Exp Med
. 2015 Aug;236(4):297–304.
24.
Wang K, Diao F, Ye Z, Zhang X, Zhai E, Ren H, et al. Prognostic value of systemic immune-inflammation index in patients with gastric cancer.
Chin J Cancer
. 2017 Sep;36(1):75.
25.
Yu J, Wu X, Yu H, Li S, Mao L, Chi Z, et al. Systemic immuneinflammation index and circulating T-cell immune index predict outcomes in high-risk acral melanoma patients treated with high-dose interferon.
Transl Oncol
. 2017 Oct;10(5):719–25.
26.
Seruga B, Zhang H, Bernstein LJ, Tannock IF. Cytokines and their relationship to the symptoms and outcome of cancer.
Nat Rev Cancer
. 2008 Nov;8(11):887–99.
27.
Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B, Bourdeau F, Kubes P, Ferri L. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis.
J Clin Invest
. 2013 Jul;pii:67484.
28.
Zheng L, Zou K, Yang C, Chen F, Guo T, Xiong B. Inflammation-based indexes and clinicopathologic features are strong predictive values of preoperative circulating tumor cell detection in gastric cancer patients.
Clin Transl Oncol
. 2017 Sep;19(9):1125–32.
29.
Lolli C, Caffo O, Scarpi E, Aieta M, Conteduca V, Maines F, et al. Systemic immune-inflammation index predicts the clinical outcome in patients with mCRPC treated with abiraterone.
Front Pharmacol
. 2016 Oct;7:376.
30.
Lolli C, Basso U, Derosa L, Scarpi E, Sava T, Santoni M, et al. Systemic immune-inflammation index predicts the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib.
Oncotarget
. 2016 Aug;7(34):54564–71.
31.
Fankhauser CD, Sander S, Roth L, Gross O, Eberli D, Sulser T, et al. Systemic inflammatory markers have independent prognostic value in patients with metastatic testicular germ cell tumours undergoing first-line chemotherapy.
Br J Cancer
. 2018 Mar;118(6):825–30.
32.
Chovanec M, Cierna Z, Miskovska V, Machalekova K, Kalavska K, Rejlekova K, et al. Systemic immune-inflammation index in germ-cell tumours.
Br J Cancer
. 2018 Mar;118(6):831–8.
33.
Albany C. Systemic immune-inflammation index in germ-cell tumours: search for a biological prognostic biomarker.
Br J Cancer
. 2018 Mar;118(6):761–2.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.