Easily Available Blood Test Neutrophil-To-Lymphocyte Ratio Predicts Progression in High-Risk Non-Muscle Invasive Bladder Cancer

Open access


Introduction: The inflammatory response surrounding the tumour has a major importance in the oncologic outcome of bladder cancers. One marker proved to be useful and accessible is NLR (neutrophil-to-lymphocyte ratio). The objective of the study was the analysis of NLR as a prognostic factor for recurrence and progression in pT1a and pT1b bladder cancers.

Material and Methods: Retrospective study, with 44 T1a/T1b bladder cancer patients. Each patient underwent transurethral resection. NLR was considered altered if higher than 3, average follow-up period was of 18 months.

Results: The mean age of the patients included was 73 years (IQR 64 - 77). Most of the patients had NLR<3 (30 patients). In total 29/44 (65.9 %) patients presented recurrence and 15/44 (34.1 %) patients were identified with T2 or higher stage progression during the follow-up period (average 18 months).We found no statistically significant association between NLR>3 and other clinic and pathologic factors. Progression-free survival (PFS) Kaplan-Meier analysis showed a lower PFS in the NLR>3 group, with a p=0.001 value. A total of 64.3% of patients had shown progression in the NLR>3 group and 20% in the NLR<3 group. Mean NLR was 2.67 (IQR 1.88-3.5); 2.50 (IQR 1.89-2.87) in patients that did not present any progression during the follow-up and 3.20 (IQR 1.73-5.80) in those with progression (p=0.09), ROC 0.655. Mean NLR was 2.14 (IQR 1.61-2.77) in patients that did not experience a recurrence during the follow-up and 2.76 (IQR 2.1-4.31) in those with recurrence, ROC 0.671 (p=0.06). Multivariable Cox regression analyses showed that stage T1b and NLR represent independent prognostic factors for PFS.

Conclusion: High Neutrophil-to-Lymphocyte ratio retained a statistically significant value, as an independent prognostic factor for bad prognosis of T1 bladder tumors. NLR represents a biomarker that could support a clinical decision making in case of high-risk on-muscle invasive bladder cancer.

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. DOI: 10.3322/caac.21262

2. Sobin LH, Gospodariwicz M, Wittekind C. TNM classification of malignant tumors [Internet]. 7th ed. Vol. UICC International Union Agains Cancer. Wiley- Blackwell; 2009. 262-265 p. Available from: http:// www.uicc.org/tnm

3. Hadadi L., Sus Ioana, Lakatos Eva Katalin, Serban Razvan Constantin, Scridon Alina, Demjen Zoltan, et al. Platelet indices and platelet-to-lymphocyte ratio predict coronary chronic total occlusion in patients with acute ST-elevation myocardial infarction. Rev Romana Med Lab. 2015;23(4):407-14. DOI: 10.1515/rrlm-2015-0041

4. Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Oca-a A, et al. Prognostic role of neutrophil- to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014 Jun;106(6):dju124. DOI: 10.1093/jnci/dju124

5. Vartolomei MD, Mathieu R, Margulis V, Karam JA, Rouprêt M, Lucca I, et al. Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy. World J Urol. 2017;35(1):121-30. DOI: 10.1007/s00345-016-1848-9

6. Ertas IE, Gungorduk K, Akman L, Ozdemir A, Terek MC, Ozsaran A, et al. Can preoperative neutrophil: lymphocyte and platelet:lymphocyte ratios be used as predictive markers for lymph node metastasis in squamous cell carcinoma of the vulva? Eur J Obstet Gynecol Reprod Biol. 2013 Nov;171(1):138-42. DOI: 10.1016/j.ejogrb.2013.08.023

7. 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. 2016 Nov;34(11):483.e17-483.e24. DOI: 10.1016/j.urolonc. 2016.05.013

8. Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer. 2013 Jul 23;109(2):416-21. DOI: 10.1038/bjc.2013.332

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. DOI: 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 Dec;190(6):1999-2004. DOI: 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 Mar;35(3):337-353. DOI: 10.1007/s00345-016-1826-2

12. Mathieu R, Vartolomei MD, Mbeutcha A, Karakiewicz PI, 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 Aug;68(4):381-95.

13. Favilla V, Castelli T, Urzì D, Reale 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 Aug;42(4):685-93. DOI: 10.1590/S1677-5538. IBJU.2015.0243

14. Babjuk M, Bohle, A., Burger M, Comperat E, Kaasinen E, Palou J, et al. Guidelines on non-muscle-invasive Bladder Cancer (Ta,T1 and CIS). In: EAU Guidelines. European Association of Urology; 2015.

15. Sylvester RJ, van der Meijden APM, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006 Mar;49(3):466-77. DOI: 10.1016/j. eururo.2005.12.031

16. Vartolomei MD, Balan D, Stefan AS, Tilinca MC, Voidezan S, Chibelean C, et al. 169 Long term follow-up after TUR-B for NMIBC. An external validation of EORTC risk tables. Eur Urol Suppl. 2015;14(5):e169.

17. Orsola A, Werner L, de Torres I, Martin-Doyle W, Raventos CX, Lozano F, et al. Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients. Br J Cancer. 2015 Feb 3;112(3):468-74. DOI: 10.1038/bjc.2014.633

18. Rouprêt M, Seisen T, Compérat E, Larré S, Mazerolles C, Gobet F, et al. Prognostic interest in discriminating muscularis mucosa invasion (T1a vs T1b) in nonmuscle invasive bladder carcinoma: French national multicenter study with central pathology review. J Urol. 2013 Jun;189(6):2069-76. DOI: 10.1016/j.juro.2012.11.120

19. 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 Dec;66(6):1157-64. DOI: 10.1016/j.eururo.2014.02.042

20. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. DOI: 10.1016/j.cell.2011.02.013

21. De Larco JE, Wuertz BRK, Furcht LT. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res Off J Am Assoc Cancer Res. 2004 Aug 1;10(15):4895-900. DOI: 10.1158/1078-0432.CCR-03-0760

22. Ferro M, De Cobelli O, Buonerba C, Di Lorenzo G, Capece M, Bruzzese D, et al. Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy: A Multicenter Experience. Medicine (Baltimore). 2015 Oct;94(42):e1861. DOI: 10.1097/ MD.0000000000001861

23. Ferro M, Giuberti G, Zappavigna S, Perdonà S, Facchini G, Sperlongano P, et al. Chondroitin sulphate enhances the antitumor activity of gemcitabine and mitomycin- C in bladder cancer cells with different mechanisms. Oncol Rep. 2012 Feb;27(2):409-15.

24. Madeb R, Golijanin D, Noyes K, Fisher S, Stephenson JJ, Long SR, et al. Treatment of nonmuscle invading bladder cancer: do physicians in the United States practice evidence based medicine? The use and economic implications of intravesical chemotherapy after transurethral resection of bladder tumors. Cancer. 2009 Jun 15;115(12):2660-70. DOI: 10.1002/cncr.24311

25. Chamie K, Saigal CS, Lai J, Hanley JM, Setodji CM, Konety BR, et al. Compliance with guidelines for patients with bladder cancer: variation in the delivery of care. Cancer. 2011 Dec 1;117(23):5392-401. DOI: 10.1002/cncr.26198

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information

IMPACT FACTOR 2017: 0.400
5-year IMPACT FACTOR: 0.320

CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2017: 0.144
Source Normalized Impact per Paper (SNIP) 2017: 0.195

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 134 134 12
PDF Downloads 65 65 3