Does neutrophil-lymphocyte ratio show recurrence in patients who underwent curative resection for non-muscle-invasive bladder cancer?

Yıl 2019, Cilt: 3 Sayı: 4, 324 - 327, 28.04.2019

Sinan Çelen , Kadir Ömür Günseren Yusuf Özlülerden , Aslı Mete , Ömer Levent Tuncay , İsmet Yavaşcaoğlu

https://doi.org/10.28982/josam.557054

Cited By: 3

Öz

Aim: The role of inflammation is a critical component of tumor progression and the neutrophil-lymphocyte ratio (NLR) reflects inflammatory status. We aimed to determine the clinical significance of the preoperative NLR in patients with non-muscle-invasive bladder cancer (NMIBC). 

Methods: A total of 178 patients, who underwent curative transurethral resection of bladder tumor (TURBT) for NMIBC between 2011 and 2016 in the urology department of Pamukkale University and Uludağ University were included in the study. Data including clinical characteristics, surgery, pathology, and follow-up were obtained from a retrospectively maintained database. Patients were divided into groups according to pre-operative NLR values (h-NLR group: ≥2.5, l-NLR group: NLR <2.5). Their cut-off values were determined through receiver operation characteristics curves analysis. Recurrence rates of the patients were determined in the 1st year follow-up. For further analysis, all of the patients were allocated according to their risk ratio according to European Organization for Research and Treatment of Cancer (EORTC) tables as low, intermediate and high, and all of the groups have been evaluated according to the risk ratio. 

Results: NLR patients (55.6% of the cases) were associated with worse risk of bladder cancer recurrence as compared to l-NLR group (P=0.005). Kaplan-Meier plots illustrated that higher pre-operative NLR had decreased disease-free survival (DFS). Low pre-operative PLR and NLR levels correlated with recurrence. 

Conclusion: The present research shows that NLR is a prognostic indicator in NMIBC. Calculating NLR value might be useful at predicting recurrence in NMIBC patients.

Anahtar Kelimeler

Bladder cancer, Recurrence, Neutrophil-lymphocyte ratio

Nötrofil lenfosit oranı, küratif rezeksiyon ile tedavi edilen yüzeyel mesane kanserinde rekürrensi gösterir mi?

Öz

Amaç: Enflamasyon, tümörün ilerlemesinin kritik bir bileşenidir ve nötrofil lenfosit oranı (NLR), enflamasyonun bir göstergesidir. Bu araştırmanın amacı; NLR'nin yüzeyel mesane kanserinde (NMIBC) prognostik bir gösterge olup olmadığını göstermekdir. 

Yöntemler: Pamukkale ve Uludağ Üniversitesi Üroloji Anabilim Dalları'nda 2011-2016 yılları arasında yüzeyel mesane kanseri nedeni ile, sadece küratif amaçlı transüretral mesane rezeksiyonu uygulanan (TUR-M) toplam 178 hasta çalışmaya dahil edildi. Hastaların klinik ve patolojik verileri retrospektif olarak incelendi. Ameliyat öncesi nötrofil/lenfosit oranına (NLR) göre NLR ≥2.5 (h-NLR) ve <2.5 (l-NLR) olacak şekilde iki gruba ayrıldı. Ayrıca hastalar daha ileri analiz için, Avrupa Üroloji Derneği risk sınıflamasına göre düşük, orta ve yüksek riskli mesane tümörü olarak alt gruplara bölündü ve kendi içinde ayrıca değerlendirildi. 1. Yıl sonunda nüks oranları belirlendi ve rekürrens oranlarına göre istatiksel analiz uygulandı. NLR 2,5 cut-off değerine göre toplam hastalıksız geçen süre Kaplan Meier eğrisi kullanılarak analiz edildi. 

Bulgular: Yapılan değerlendirmeler ile h-NLR hastaları (%55,6), l-NLR hastalarına göre istatiksel anlamlı olarak yüksek rekürrens oranlarına sahipti (P=0.005). Kaplan-Meier analizi sonucunda, h-NLR'nin hastalıksız geçen süreyi önemli ölçüde azalttığını ve rekürrensi arttırdığını göstermiştir. 

Sonuç: NLR'nin, NMIBC hastalarında tümör rekürrensi değerlendirmesinde kullanılabilecek, faydalı bir biyobelirteç gibi görünmektedir.

Anahtar Kelimeler

Mesane kanseri, Rekürrens, Nötrofil-lenfosit oranı

Kaynakça

• 1. Gkritsios P, Hatzimouratidis K, Kazantzidis S, Dimitriadis G, Ioannidis E, Katsikas V. Hexaminolevulinate-guided transurethral resection of non-muscle-invasive bladder cancer does not reduce the recurrence rates after a 2-year follow-up: a prospective randomized trial. Int Urol Nephrol. 2014;46:927-33.
• 2. Can C, Baseskioglu B, Yılmaz M, Colak E, Ozen A, Yenilmez A. Pretreatment parameters obtained from peripheral blood sample predicts invasiveness of bladder carcinoma. Urol Int. 2012;89:468-72.
• 3. Sylvester RJ 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;49:466-5.
• 4. van Rhijn BW. et al. Molecular grade (FGFR3/MIB- 1) and EORTC risk scores are predictive in primary nonmuscle- invasive bladder cancer. Eur Urol. 2010;58:433-41.
• 5. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Current Opinion in Clinical Nutrition and Metabolic Care. 2009;12(3):223-6.
• 6. Proctor MJ. et al. A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer. 2011;47(17):2633-41.
• 7. Roxburgh CS, Salmond JM, Horgan PG, Oien KA, McMillan DC. Comparison of the prognostic value of inflammation based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Annals of Surgery. 2009;249(5):788-93.
• 8. Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. Journal of Surgical Oncology. 2005;91(3):181-4.
• 9. Gwak MS et al. Effects of gender on white blood cell populations and neutrophil-lymphocyte ratio following gastrectomy in patients with stomach cancer. Journal of Korean Medical Science. 2007;22 Suppl:S104-8.
• 10. Dobbs RW, Hugar LA, Revenig LM, Al-Qassab S, Petros JA, Ritenour CW, et al. Incidence and clinical characteristics of lower urinary tract symptoms as a presenting symptom for patients with newly diagnosed bladder cancer. Int Braz J Urol. 2014 Mar-Apr;40(2):198-203.
• 11. Odisho AY, Berry AB, Ahmad AE, Cooperberg MR, Carroll PR, Konety BR. Reflex ImmunoCyt testing for the diagnosis of bladder cancer in patients with atypical urine cytology. Eur Urol. 2013;63:936-40.
• 12. Têtu B, Tiguert R, Harel F, Fradet Y. ImmunoCyt/uCyt+ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma. Mod Pathol. 2005;18:83-9.
• 13. Shariat SF, Chromecki TF, Cha EK, Karakiewicz PI, Sun M, Fradet Y, et al. Risk stratification for bladder tumor recurrence, stage and grade by urinary nuclear matrix protein 22 and cytology. Eur Urol. 2004;45:304-13.
• 14. Sokolova IA, Halling KC, Jenkins RB, Burkhardt HM, Meyer RG, Seelig SA, et al. The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine. J Mol Diagn. 2000;2:116-23.
• 15. Bryan RT, Regan HL, Pirrie SJ, Devall AJ, Cheng KK, Zeegers MP, et al. Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM. Br J Cancer. 2015;112:1052-8.
• 16. Kelloff GJ, Sigman CC, Scher HI. Biomarker development in the context of urologic cancers. Urol Oncol. 2015;33:295-301.
• 17. Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology. 2007;73:215-20.
• 18. Cho H ,Hur HW, Kim SW, Kim SH, Kim JH, Kim YT, et al. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother. 2009;58:15-23.
• 19. Yıldırım ÖT, Akşit E, Aydın F, Aydın AH, Dağtekin E. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio can be used as biomarkers for non-dipper blood pressure. J Surg Med. 2019;3(1):4-7.
• 20. Küçük U, Arslan M. Assessment of the white blood cell subtypes ratio in patients with supraventricular tachycardia: Retrospective cohort study. J Surg Med. 2019;3(4):297-9.
• 21. 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. 2014;32:631-6.
• 22. Hermanns T, Bhindi B, Wei Y, Yu J, Noon AP, Richard PO, et al. Pre-treatment neutrophil-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Br J Cancer. 2014;111:444-51.
• 23. Viers BR, Boorjian SA, Frank I, Tarrell RF, Thapa P, Karnes RJ, et al. Pretreatment neutrophil-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;66:1157-64.
• 24. Tachibana M, Miyakawa A, Tazaki H, Nakamura K, Kubo A, Hata J, et al. Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor. Cancer Res. 1995;55:3438-43.
• 25. Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6:283-7.
• 26. Gondo T, Nakashima J, Ohno Y, Choichiro O, Horiguchi Y, Namiki K, et al. Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology. 2012;79:1085-91.
• 27. 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;27:1046-50.
• 28. Marchioni M, Primiceri G, Ingrosso M, Filograna R, Castellan P, De Francesco P, et al. The clinical use of the neutrophil-lymphocyte ratio (NRL) in urothelial cancer: A systematic review. Clin Genitourin Cancer. 2016;14:473-84.
• 29. Marchioni M, Primiceri G, Ingrosso M, Filograna R, Castellan P, De Francesco P, et al. Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non-muscle-invasive bladder cancer. Urol Oncol. 2015;33:67.e1-7.