Predictive value of neutrophil-to-lymphocyte ratio prior to transurethral resection for muscle invasion in bladder cancer

Öz

Aim: To evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) before transurethral resection in determining muscle invasion in patients diagnosed with bladder cancer. Materials and Methods: This retrospective study included patients who underwent first-time transurethral resection of bladder tumors (TUR-B) for primary bladder cancer between January 2016 and December 2024. Patients with carcinoma in situ, preoperative infection, hematologic malignancies, or unexplained leukocytosis were excluded. Patients were divided into two groups based on pathological staging: Group 1 (pTa/pT1) and Group 2 (pT2). Demographic, clinical, and laboratory parameters, including leukocyte, neutrophil, and lymphocyte counts, were recorded. The optimal NLR cutoff for predicting muscle invasion was determined using ROC analysis. Statistical analyses were performed using IBM Statistical Package for Social Sciences (SPSS) program software with a significance threshold of p <0.05. Results: A total of 731 patients were included. Muscle invasion (pT2) was identified in 129 patients (17.6%). Group 2 had significantly higher age, proportion of female patients, high-grade tumors, and tumors larger than 3 cm. Lymphocyte counts were significantly lower in Group 2, while leukocyte, neutrophil counts, and NLR were significantly higher (p<0.001 for all). The optimal cutoff value of NLR was 2.96 (sensitivity: 42.6%, specificity: 89.5%, AUC: 0.701). Logistic regression revealed that female sex, high tumor grade, tumor size, and elevated NLR were independently associated with muscle invasion. Conclusion: Preoperative neutrophil-to-lymphocyte ratio (NLR) is significantly associated with muscle-invasive bladder cancer. As a simple and accessible inflammatory marker, NLR may support preoperative staging and inform clinical decision-making in bladder cancer management.

Anahtar Kelimeler

• bladder cancer
• lymphocyte
• muscle invasion
• neutrophil

Kaynakça

1. 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492
2. 2. Cumberbatch M, 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):784–795. https://doi.org/10.1016/j.eururo.2018.09.001
3. 3. Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, et al. Treatment of nonmetastatic muscle-invasive bladder cancer: American Urological Association/American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Urologic Oncology clinical practice guideline summary. J Oncol Pract. 2017;13:621–625. https://doi.org/10.1200/JOP.2017.024919
4. 4. Ark JT, Keegan KA, Barocas DA, Morgan TM, Resnick MJ, You C, et al. Incidence and predictors of understaging in patients with clinical T1 urothelial carcinoma undergoing radical cystectomy. BJU Int. 2014;113:894–899. https://doi.org/10.1111/bju.12245
5. 5. Guthrie GJ, Charles KA, Roxburgh CS, 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):218–230. https://doi.org/10.1016/j.critrevonc.2013.03.010
6. 6. Getzler I, Bahouth Z, Nativ O, Rubinstein J, Halachmi S. Preoperative neutrophil to lymphocyte ratio improves recurrence prediction of non-muscle invasive bladder cancer. BMC Urol. 2018;18(1):1–10. https://doi.org/10.1186/s12894-018-0404-x
7. 7. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–899. https://doi.org/10.1016/j.cell.2010.01.025
8. 8. Madonia M, Paliogiannis P, Solinas T, Mangoni AA, Carru C, Zinellu A. Neutrophil to lymphocyte ratio and muscular invasion in early-stage bladder cancer: a meta-analysis. Eur J Oncol. 2018;23:65–71.

9. 9. Guthrie GJ, Charles KA, Roxburgh CS, 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):218–230. https://doi.org/10.1016/j.critrevonc.2013.03.010
10. 10. Li X, Ma X, Tang L, Wang B, Chen L, Zhang F, et al. Prognostic value of neutrophil to-lymphocyte ratio in urothelial carcinoma of the upper urinary tract and bladder: a systematic review and meta analysis. Oncotarget. 2016;8:62681–62692. https://doi.org/10.18632/oncotarget.17467
11. 11. Margetts J, Ogle LF, Chan SL, Chan AW, Chan KC, Jamieson D, et al. Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma? Br J Cancer. 2018;118:248–257. https://doi.org/10.1038/bjc.2017.386
12. 12. Mitra AP, Cai J, Miranda G, Bhanvadia S, Quinn DI, Schuckman AK, et al. Management trends and outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder: evolution of the University of Southern California Experience over 3,347 Cases. J Urol. 2022;207:302–313. https://doi.org/10.1097/JU.0000000000002242
13. 13. 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;106(6):124–135. https://doi.org/10.1093/jnci/dju124
14. 14. Yi M, Li T, Niu M, Mei Q, Zhao B, Chu Q, et al. Exploiting innate immunity for cancer immunotherapy. Mol Cancer. 2023;22:187–242. https://doi.org/10.1186/s12943-023-01885-w
15. 15. Hassan WA, ElBanna AK, Noufal N, El-Assmy M, Lotfy H, Ali RI. Significance of tumor-associated neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio in non-invasive and invasive bladder urothelial carcinoma. J Pathol Transl Med. 2023;57(2):88–94. https://doi.org/10.4132/jptm.2022.11.06