Advertisement

The prognostic role of preoperative circulating neutrophil–lymphocyte ratio in primary bladder cancer patients undergoing radical cystectomy: a meta-analysis

  • Guoming Hu
  • Feng Xu
  • Kefang Zhong
  • Shimin Wang
  • Qi Xu
  • Liming Huang
  • Pu Cheng
Original Article

Abstract

Background

Systemic inflammatory response (SIR) plays important roles in initiation, promotion and progression of tumor. However, the prognostic role of preoperative circulating neutrophil–lymphocyte ratio (NLR) (known as a marker of SIR) in human primary bladder cancer (BC) undergoing radical cystectomy (RC) remains controversial. Hence, we performed this meta-analysis to better understand the role of preoperative circulating NLR in prognosis prediction for primary BC patients undergoing RC.

Methods

We searched PubMed, Embase and EBSCO to identify the studies and computed extracted data with STATA 12.0.

Results

A total of 11,945 patients with BC from 18 published studies were incorporated into this meta-analysis. We found that elevated NLR was significantly associated with decreased 3-year and 5-year overall survival (OS), 1-year, 3-year and 5-year recurrence-free survival (RFS), but not with 1-year or 10-year OS, or 10-year RFS in primary BC patients who underwent RC. The results also showed that neoadjuvant chemotherapy (NAC) had a significant impact on the negative prognostic effect of NLR. In addition, high NLR significantly correlated with unfavorable clinicopathological features of BC.

Conclusion

Elevated preoperative circulating NLR leads to an unfavorable outcome in primary BC undergoing RC, especially in patients without NAC, implicating that it might be a valuable prognostic index for these patients.

Keywords

Preoperative circulating neutrophil–lymphocyte ratio Unfavorable outcome Primary bladder cancer Radical cystectomy Neoadjuvant chemotherapy Meta-analysis 

Abbreviations

NLR

Neutrophil–lymphocyte ratio

SIR

Systemic inflammatory response

BC

Bladder cancer

RC

Radical cystectomy

NAC

Neoadjuvant chemotherapy

OS

Overall survival

RFS

Recurrence-free survival

HR

Hazard rations

OR

Odds ratios

Cl

Confidence interval

TNM

Tumor, lymph node, metastasis

NR

Not reported

Notes

Acknowledgements

We thank all the members of the departments who helped in this study.

Author contributions

GH contributed to protocol and project development, data collection and manuscript writing; FX, QX and KZ contributed to data collection; SW and LH contributed to data analysis; PC contributed to protocol and project development and the manuscript revision. All authors read and approved the final manuscript.

Funding

This work was funded by the National Natural Science Foundation of China (Grant no. 81702803, GMH).

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.

Research involving human participants and/or animals

Human participants.

Informed consent

The ethical approval was unnecessary because this study based on summary and analysis of the results of previous studies.

Supplementary material

345_2018_2593_MOESM1_ESM.pdf (657 kb)
Supplementary material 1 (PDF 657 kb)

References

  1. 1.
    Albayrak S, Zengin K, Tanik S, Atar M, Unal SH, Imamoglu MA, Gurdal M (2016) Can the neutrophil-to-lymphocyte ratio be used to predict recurrence and progression of non-muscle-invasive bladder cancer? Kaohsiung J Med Sci 32:327–333CrossRefPubMedGoogle Scholar
  2. 2.
    Stang A (2010) Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kuritz SJ, Landis JR, Koch GG (1988) A general overview of Mantel–Haenszel methods: applications and recent developments. Annu Rev Public Health 9:123–160CrossRefPubMedGoogle Scholar
  5. 5.
    DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114CrossRefPubMedGoogle Scholar
  6. 6.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    D’Andrea D, Moschini M, Gust KM, Abufaraj M, Ozsoy M, Mathieu R, Soria F, Briganti A, Roupret M, Karakiewicz PI, Shariat SF (2017) Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio as biomarkers for predicting lymph node metastasis and survival in patients treated with radical cystectomy. J Surg Oncol 115:455–461CrossRefPubMedGoogle Scholar
  8. 8.
    Zhang GM, Zhu Y, Luo L, Wan FN, Zhu YP, Sun LJ, Ye DW (2015) Preoperative lymphocyte-monocyte and platelet-lymphocyte ratios as predictors of overall survival in patients with bladder cancer undergoing radical cystectomy. Tumour Biol 36:8537–8543CrossRefPubMedGoogle Scholar
  9. 9.
    Kang M, Jeong CW, Kwak C, Kim HH, Ku JH (2016) The prognostic significance of the early postoperative neutrophil-to-lymphocyte ratio in patients with urothelial carcinoma of the bladder undergoing radical cystectomy. Ann Surg Oncol 23:335–342CrossRefPubMedGoogle Scholar
  10. 10.
    Viers BR, Boorjian SA, Frank I, Tarrell RF, Thapa P, Karnes RJ, Thompson RH, Tollefson MK (2014) 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 66:1157–1164CrossRefPubMedGoogle Scholar
  11. 11.
    Ogihara K, Kikuchi E, Yuge K, Yanai Y, Matsumoto K, Miyajima A, Asakura H, Oya M (2016) The preoperative neutrophil-to-lymphocyte ratio is a novel biomarker for predicting worse clinical outcomes in non-muscle invasive bladder cancer patients with a previous history of smoking. Ann Surg Oncol 23:1039–1047CrossRefPubMedGoogle Scholar
  12. 12.
    Favilla V, Castelli T, Urzi D, Reale G, Privitera S, Salici A, Russo GI, Cimino S, Morgia G (2016) Neutrophil to lymphocyte ratio, a biomarker in non-muscle invasive bladder cancer: a single-institutional longitudinal study. Int Braz J Urol 42:685–693CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mano R, Baniel J, Shoshany O, Margel D, Bar-On T, Nativ O, Rubinstein J, Halachmi S (2015) Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non-muscle-invasive bladder cancer. Urol Oncol 33(67):e1–e7Google Scholar
  14. 14.
    Ojerholm E, Smith A, Hwang WT, Baumann BC, Tucker KN, Lerner SP, Mamtani R, Boursi B, Christodouleas JP (2017) Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: assessing prognostic and predictive value in SWOG 8710. Cancer 123:794–801CrossRefPubMedGoogle Scholar
  15. 15.
    Hermanns T, Bhindi B, Wei Y, Yu J, Noon AP, Richard PO, Bhatt JR, Almatar A, Jewett MA, Fleshner NE, Zlotta AR, Templeton AJ, Kulkarni GS (2014) 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 111:444–451CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kawahara T, Furuya K, Nakamura M, Sakamaki K, Osaka K, Ito H, Ito Y, Izumi K, Ohtake S, Miyoshi Y, Makiyama K, Nakaigawa N, Yamanaka T, Miyamoto H, Yao M, Uemura H (2016) Neutrophil-to-lymphocyte ratio is a prognostic marker in bladder cancer patients after radical cystectomy. BMC Cancer 16:185CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hirasawa Y, Nakashima J, Yunaiyama D, Sugihara T, Gondo T, Nakagami Y, Horiguchi Y, Ohno Y, Namiki K, Ohori M, Tokuuye K, Tachibana M (2016) Sarcopenia as a novel preoperative prognostic predictor for survival in patients with bladder cancer undergoing radical cystectomy. Ann Surg Oncol 23:1048–1054CrossRefPubMedGoogle Scholar
  18. 18.
    Kang M, Jeong CW, Kwak C, Kim HH, Ku JH (2017) Preoperative neutrophil-lymphocyte ratio can significantly predict mortality outcomes in patients with non-muscle invasive bladder cancer undergoing transurethral resection of bladder tumor. Oncotarget 8:12891–12901PubMedGoogle Scholar
  19. 19.
    Ozcan C, Telli O, Ozturk E, Suer E, Gokce MI, Gulpinar O, Oztuna D, Baltaci S, Gogus C (2015) The prognostic significance of preoperative leukocytosis and neutrophil-to-lymphocyte ratio in patients who underwent radical cystectomy for bladder cancer. Can Urol Assoc J 9:E789–E794CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Buisan O, Orsola A, Areal J, Font A, Oliveira M, Martinez R, Ibarz L (2017) Low pretreatment neutrophil-to-lymphocyte ratio predicts for good outcomes in patients receiving neoadjuvant chemotherapy before radical cystectomy for muscle invasive bladder cancer. Clin Genitourin Cancer 15:145–151 e2CrossRefPubMedGoogle Scholar
  21. 21.
    Morizawa Y, Miyake M, Shimada K, Hori S, Tatsumi Y, Nakai Y, Anai S, Tanaka N, Konishi N, Fujimoto K (2016) Neutrophil-to-lymphocyte ratio as a detection marker of tumor recurrence in patients with muscle-invasive bladder cancer after radical cystectomy. Urol Oncol 34(257):e11–e17Google Scholar
  22. 22.
    Tan YG, Eu E, Lau Kam On W, Huang HH (2017) Pretreatment neutrophil-to-lymphocyte ratio predicts worse survival outcomes and advanced tumor staging in patients undergoing radical cystectomy for bladder cancer. Asian J Urol 4:239–246CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gondo T, Nakashima J, Ohno Y, Choichiro O, Horiguchi Y, Namiki K, Yoshioka K, Ohori M, Hatano T, Tachibana M (2012) Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology 79:1085–1091CrossRefPubMedGoogle Scholar
  24. 24.
    Yoshida T, Kinoshita H, Yoshida K, Mishima T, Yanishi M, Komai Y, Sugi M, Murota T, Kawa G, Matsuda T (2016) Perioperative change in neutrophil-lymphocyte ratio predicts the overall survival of patients with bladder cancer undergoing radical cystectomy. Jpn J Clin Oncol 46:1162–1167CrossRefPubMedGoogle Scholar
  25. 25.
    Ozyalvacli ME, Ozyalvacli G, Kocaaslan R, Cecen K, Uyeturk U, Kemahli E, Gucuk A (2015) Neutrophil-lymphocyte ratio as a predictor of recurrence and progression in patients with high-grade pT1 bladder cancer. Can Urol Assoc J 9:E126–E131CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    van Kessel KE, de Haan LM, Fransen van de Putte EE, van Rhijn BW, de Wit R, van der Heijden MS, Zwarthoff EC, Boormans JL (2016) Elevated derived neutrophil-to-lymphocyte ratio corresponds with poor outcome in patients undergoing pre-operative chemotherapy in muscle-invasive bladder cancer. Bladder Cancer 2:351–360CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Buisan O, Orsola A, Oliveira M, Martinez R, Etxaniz O, Areal J, Ibarz L (2017) Role of inflammation in the perioperative management of urothelial bladder cancer with squamous-cell features: impact of neutrophil-to-lymphocyte ratio on outcomes and response to neoadjuvant chemotherapy. Clin Genitourin Cancer 14:e697–e706CrossRefGoogle Scholar
  28. 28.
    Krane LS, Richards KA, Kader AK, Davis R, Balaji KC, Hemal AK (2013) Preoperative neutrophil/lymphocyte ratio predicts overall survival and extravesical disease in patients undergoing radical cystectomy. J Endourol 27:1046–1050CrossRefPubMedGoogle Scholar
  29. 29.
    Mbeutcha A, Shariat SF, Rieken M, Rink M, Xylinas E, Seitz C, Lucca I, Mathieu R, Roupret M, Briganti A, Karakiewicz PI, Klatte T (2016) Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer. Urol Oncol 34:483 e17–483 e24CrossRefGoogle Scholar
  30. 30.
    D’Andrea D, Moschini M, Gust K, Abufaraj M, Ozsoy M, Mathieu R, Soria F, Briganti A, Roupret M, Karakiewicz PI, Shariat SF (2017) Prognostic role of neutrophil-to-lymphocyte ratio in primary non-muscle-invasive bladder cancer. Clin Genitourin Cancer 15:e755–e764CrossRefPubMedGoogle Scholar
  31. 31.
    Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Li X, Ma X, Tang L, Wang B, Chen L, Zhang F, Zhang X (2017) Prognostic value of neutrophil-to-lymphocyte ratio in urothelial carcinoma of the upper urinary tract and bladder: a systematic review and meta-analysis. Oncotarget 8:62681–62692PubMedGoogle Scholar
  33. 33.
    Lucca I, Jichlinski P, Shariat SF, Roupret M, Rieken M, Kluth LA, Rink M, Mathieu R, Mbeutcha A, Maj-Hes A, Fajkovic H, Briganti A, Seitz C, Karakiewicz PI, de Martino M, Lotan Y, Babjuk M, Klatte T (2016) 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 2:79–85CrossRefPubMedGoogle Scholar
  34. 34.
    Tang X, Du P, Yang Y (2017) The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis. Int J Clin Oncol 22:817–825CrossRefPubMedGoogle Scholar
  35. 35.
    Tachibana M, Miyakawa A, Tazaki H, Nakamura K, Kubo A, Hata J, Nishi T, Amano Y (1995) Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor. Cancer Res 55:3438–3443PubMedGoogle Scholar
  36. 36.
    Swierczak A, Mouchemore KA, Hamilton JA, Anderson RL (2015) Neutrophils: important contributors to tumor progression and metastasis. Cancer Metastasis Rev 34:735–751CrossRefPubMedGoogle Scholar
  37. 37.
    Uribe-Querol E, Rosales C (2015) Neutrophils in cancer: two sides of the same coin. J Immunol Res 2015:983698CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of General Surgery (Breast and Thyroid Surgery)Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)ShaoxingChina
  2. 2.Department of NephrologyShaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)ShaoxingChina
  3. 3.Department of Surgical OncologyShaoxing Second HospitalShaoxingChina
  4. 4.Department of Gynecology, Second Affiliated Hospital, Zhejiang University School of MedicineZhejiang UniversityHangzhouChina

Personalised recommendations