Correlation of neutrophil ratio to lymphocyte levels before therapy with the incidence of metastasis, lymph node involvements, in urothelial type muscle invasive bladder cancer in Indonesia

https://doi.org/10.19106/JMedSci005403202208

Rudi Rafian(1), Ahmad Zulfan Hendri(2), Indrawarman Soerohardjo(3), Raden Danarto(4*)

(1) Division of Urology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
(2) Division of Urology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
(3) Division of Urology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
(4) Division of Urology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
(*) Corresponding Author

Abstract


Bladder cancer is cancer originated from the bladder mucosa or urothelium. Bladder cancer is the 9th most common malignancy worldwide and the most common malignancy of the urinary tract. Studies show that cancer triggers an inflammatory response, which causes changes in circulating inflammatory cells. Examination of neutrophils and lymphocytes is an inexpensive examination, reproducible, and easily obtained. Neutrophil to lymphocyte ratio (NLR) values have been used in several studies to evaluate the inflammatory response that occurs in tumors. In urology, the importance of NLR has been recognized in predicting progression and aggressiveness in urothelial bladder tumors, kidney cancer (RCC/renal cell carcinoma), and upper tract urothelial carcinoma (UTUC). This study was a cross-sectional study obtained retrospectively by evaluating the medical records of patients diagnosed with muscle-invasive bladder cancer (MIBC) at Dr. Sardjito General Hospital, Yogyakarta, Indonesia from January 2017 to December 2019. The NLR data were categorized into NLR < 2.5 and > 2.5. As much as 150 patients with bladder cancer were included in this study, with a mean age of 56.43 ± 13.60 years. In the comparison of NLR values and the incidence of metastasis, there were 15 people (20%) with NLR values < 2.5 who had metastasis while 32 people (42.7%) from the group with NLR > 2.5 had metastasis (p = 0.003). In the comparison of NLR values and nodule involvement, there were 25 (33.3%) patients with NLR < 2.5 and 39 (52%) patients with NLR > 2.5 (p = 0.021). This study showed that patients with metastatic bladder tumors and lymph node involvement had a significantly higher NLR value. It can be concluded the NLR value can be used to predict the metastatic level and lymph node involvement in patients with bladder tumors. Even though it is not a specific marker of inflammation, the NLR examination is simple, affordable, easy to obtain, and widely available.


Keywords


NLR; bladder cancer; metastasis; marker; renal cell carcinoma; inflammatory cells

Full Text:

PDF


References

Crawford JM. The origins of bladder cancer. Lab Invest 2008; 88(7):686-93.
https://doi.org/10.1038/labinvest.2008.48
2.Lee SM, Russell A, Hellawell G. Predictive value of pretreatment inflammation-based prognostic scores (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio) for invasive bladder carcinoma. Korean J Urol 2015; 56(11):749-55.
https://doi.org/10.4111/kju.2015.56.11.749
3.Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420(6917):860-7.
https://doi.org/10.1038/nature01322
4.Kaynar M, Yildirim ME, Badem H, Çaviş M, Tekinarslan E, Istanbulluoǧlu MO, et al. Bladder cancer invasion predictability based on preoperative neutrophil-lymphocyte ratio. Tumor Biol 2014; 35(7):6601-5.
https://doi.org/10.1007/s13277-014-1889-x
5.Favilla V, Castelli T, Urzì D, Real G, Privitera S, Salici A, et al. Neutrophil to lymphocyte ratio, a biomarker in non-muscle invasive bladder cancer: A single-institutional longitudinal study. Int Braz J Urol 2016; 42(4):685-93.
https://doi.org/10.1590/S1677-5538.IBJU.2015.0243
6.Martha O, Porav-Hodade D, Bălan D, Tătaru OS, Sin A, Chibelean CB, et al. Easily available blood test neutrophil-to-lymphocyte ratio predicts progression in high-risk non-muscle invasive bladder cancer. Rev Rom Med Lab 2017; 25(2):181-9.
https://doi.org/10.1515/rrlm-2017-0016
7.Wu S, Zhao X, Wang Y, Zhong Z, Zhang L, Cao J, . Pretreatment neutrophil-lymphocyte ratio as a predictor in bladder cancer and metastatic or unresectable urothelial carcinoma patients: a pooled analysis of comparative studies. Cell Physiol Biochem 2018; 46(4):1352-64.
https://doi.org/10.1159/000489152
8.Rajwa P, Zyczkowski M, Paradysz A, Bujak K, Bryniarski P. Evaluation of the prognostic value of LMR, PLR, NLR, and dNLR in urothelial bladder cancer patients treated with radical cystectomy. Eur Rev Med Pharmacol Sci 2018; 22(10):3027-37.
https://doi.org/10.26355/eurrev_201805_15060
9.Lucca I, Jichlinski P, Shariat SF, Rouprêt M, Rieken M, Kluth LA, et al. The neutrophil-to-lymphocyte ratio as a prognostic factor for patients with urothelial carcinoma of the bladder following radical cystectomy: validation and meta-analysis. Eur Urol Focus 2016; 2(1):79-85.
https://doi.org/10.1016/j.euf.2015.03.001
10.De Martino M, Pantuck AJ, Hofbauer S, Waldert M, Shariat SF, Belldegrun AS, et al. Prognostic impact of preoperative neutrophil-to-lymphocyte ratio in localized nonclear cell renal cell carcinoma. J Urol 2013; 190(6):1999-2004.
https://doi.org/10.1016/j.juro.2013.06.082
11.Mbeutcha A, Rouprêt M, Kamat AM, Karakiewicz PI, Lawrentschuk N, Novara G, et al. Prognostic factors and predictive tools for upper tract urothelial carcinoma: a systematic review. World J Urol 2017; 35(3):337-53.
https://doi.org/10.1007/s00345-016-1826-2
12.Mathieu R, Vartolomei MD, Mbeutcha A, Karakiewicz P, Briganti A, Roupret M, et al. Urothelial cancer of the upper urinary tract: emerging biomarkers and integrative models for risk stratification. Minerva Urol Nefrol 2016; 68(4):381-95.
13.Wu CT, Huang YC, Chen WC, Chen MF. The significance of neutrophil-to-lymphocyte ratio and combined chemoradiotherapy in patients undergoing bladder preservation therapy for muscle-invasive bladder cancer. Cancer Manag Res 2020; 12:13125-35.
https://doi.org/10.2147/CMAR.S283954
14.Wang R, Yan Y, Liu S, Yao X. Comparison of preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios in bladder cancer patients undergoing radical cystectomy. Biomed Res Int 2019; 2019:3628384.
https://doi.org/10.1155/2019/3628384
15.Kim J, Bae JS. Review article tumor-associated macrophages and neutrophils in tumor microenvironment. Mediators Inflamm 2016; 2016:6058147.
https://doi.org/10.1155/2016/6058147
16.Richards DM, Hettinger J, Feuerer M. Monocytes and macrophages in cancer: development and functions. Cancer Microenviron 2013; 6(2):179-91.
https://doi.org/10.1007/s12307-012-0123-x
17.Coffelt SB, Wellenstein MD, De Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer 2016; 16(7):431-46.
https://doi.org/10.1038/nrc.2016.52
18.Viers BR, Boorjian SA, Frank I, Tarrell RF, Thapa P, Karnes RJ, et al. Pretreatment neutrophil-to-lymphocyte ratio is associated with advanced pathologic tumor stage and increased cancer-specific mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy. Eur Urol 2014; 66(6):1157-64.
https://doi.org/10.1016/j.eururo.2014.02.042
19.Potretzke A, Hillman L, Wong K, Shi F, Brower R, Mai S, et al. NLR is predictive of upstaging at the time of radical cystectomy for patients with urothelial carcinoma of the bladder. Urol Oncol Semin Orig Investig 2014; 32(5):631-6.
https://doi.org/10.1016/j.urolonc.2013.12.009
20.Hermanns T, Bhindi B, Wei Y, Yu J, Noon AP, Richard PO, et al. Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Br J Cancer 2014; 111(3):444-51.
https://doi.org/10.1038/bjc.2014.305
21.Guthrie GJK, Charles KA, Roxburgh CSD, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol 2013; 88(1):218-30.
https://doi.org/10.1016/j.critrevonc.2013.03.010
22.Gu X, Gao X, Qin S, Li X, Qi X, Ma M, et al. Prognostic value of neutrophil to lymphocyte ratio in patients with bladder cancer : a meta-analysis. 2016; 9(11):20615-23.
23.Kim HS, Ku JH. Systemic inflammatory response based on neutrophil-to-lymphocyte ratio as a prognostic marker in bladder cancer. Dis Markers 2016; 2016:8345286.
https://doi.org/10.1155/2016/8345286
24.Tang X, Du P, Yang Y. The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis. Int J Clin Oncol 2017; 22(5):817-25.
https://doi.org/10.1007/s10147-017-1171-5
25.Mbeutcha A, Shariat SF, Rieken M, Rink M, Xylinas E, Seitz C, et al. Prognostic significance of markers of systemic inflammatory response in patients with non–muscle-invasive bladder cancer. Urol Oncol Semin Orig Investig 2016; 34(11):483.e17-24.
https://doi.org/10.1016/j.urolonc.2016.05.013
26.Krane LS, Richards KA, Kader AK, Davis R, Balaji KC, Hemal AK. Preoperative neutrophil/lymphocyte ratio predicts overall survival and extravesical disease in patients undergoing radical cystectomy. J Endourol 2013; 27(8):1046-50.
https://doi.org/10.1089/end.2012.0606
27.Tan YG, Eu E, Kam On WL, Huang HH. Pretreatment neutrophil-to-lymphocyte ratio predicts worse survival outcomes and advanced tumour staging in patients undergoing radical cystectomy for bladder cancer. Asian J Urol 2017; 4(4):239-46.
https://doi.org/10.1016/j.ajur.2017.01.004
28.Albayrak S, Zengin K, Tanik S, Atar M, Unal SH, Imamoglu MA, et al. Can the neutrophil-to-lymphocyte ratio be used to predict recurrence and progression of non-muscle-invasive bladder cancer? Kaohsiung J Med Sci 2016; 32(6):327-33.
https://doi.org/10.1016/j.kjms.2016.05.001
29.Laird BJ, McMillan DC, Fayers P, Fearon K, Kaasa S, Fallon MT, et al. The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer. Oncologist 2013; 18(9):1050-5.
https://doi.org/10.1634/theoncologist.2013-0120
30.Chen ZY, Raghav K, Lieu CH, Jiang ZQ, Eng C, Vauthey JN, et al. Cytokine profile and prognostic significance of high neutrophil-lymphocyte ratio in colorectal cancer. Br J Cancer 2015; 112(6):1088-97.
https://doi.org/10.1038/bjc.2015.61
31.Motomura T, Shirabe K, Mano Y, Muto J, Toshima T, Umemoto Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol 2013; 58(1):58-64.
https://doi.org/10.1016/j.jhep.2012.08.017
32.Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5):646-74.
https://doi.org/10.1016/j.cell.2011.02.013
33.Hermanns T, Bhindi B, Wei Y, Yu J, Noon AP, Richard PO, et al. Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Br J Cancer 2014; 111(3):444-51.
https://doi.org/10.1038/bjc.2014.305
34.Fondevila C, Metges JP, Fuster J, Grau JJ, Palacín A, Castells A, et al. p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 2004; 90(1):206-15.
https://doi.org/10.1038/sj.bjc.6601455
35.Kusumanto YH, Dam WA, Hospers GAP, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 2003; 6(4):283-7.
https://doi.org/10.1023/B:AGEN.0000029415.62384.ba
36.Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004; 21(2):137-48.
https://doi.org/10.1016/j.immuni.2004.07.017
37.Joseph N, Dovedi SJ, Thompson C, Lyons J, Kennedy J, Elliott T, et al. Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer. Ann Oncol 2016; 27(2):294-9.
https://doi.org/10.1093/annonc/mdv546
38.Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140(6):883-99.
https://doi.org/10.1016/j.cell.2010.01.025
39.Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420(6917):860-7.
https://doi.org/10.1038/nature01322
40.Maeda K, Malykhin A, Teague-weber BN, Sun XH, Farris AD, Coggeshall KM. Interleukin-6 aborts lymphopoiesis and elevates production of myeloid cells in systemic lupus erythematosus – prone B6.Sle1.Yaa animals. Blood 2009; 113(19):4534-40.
https://doi.org/10.1182/blood-2008-12-192559
41.Fisher A, Srikusalanukul W, Fisher L, Smith P. The neutrophil to lymphocyte ratio on admission and short-term outcomes in orthogeriatric patients. Int J Med Sci 2016; 13(8):588-602.
https://doi.org/10.7150/ijms.15445
42.American Society of Clinical Oncology. Bladder Cancer: Risk Factors. 10/2017. Accessed at www.cancer.net/cancer-types/bladder-cancer/risk-factors on December 6, 2018.
43.Cumberbatch MGK, Jubber I, Black PC, Esperto F, Figueroa JD, Kamat AM, et al. Epidemiology of bladder cancer: a systematic review and contemporary update of risk factors in 2018. Eur Urol 2018; 74(6):784-95.
https://doi.org/10.1016/j.eururo.2018.09.001



DOI: https://doi.org/10.19106/JMedSci005403202208

Article Metrics

Abstract views : 165 | views : 256




Copyright (c) 2022 Rudi Rafian, Raden Danarto

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

View My Stats

 

Creative Commons License
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Based on a work at http://jurnal.ugm.ac.id/bik/.