Preoperative Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker of Tumor Grade in Non–Muscle-Invasive Bladder Cancer: A Prospective Cross-Sectional Study
DOI:
https://doi.org/10.52206/jsmc.2026.16.2.1500Abstract
Background: Non–muscle-invasive bladder cancer (NMIBC) accounts for the majority of newly diagnosed bladder tumors and is associated with high recurrence and progression rates. The neutrophil-to-lymphocyte ratio (NLR), a readily available marker of systemic inflammation, has emerged as a potential prognostic biomarker in urothelial carcinoma.
Objective: To evaluate the association between preoperative neutrophil-to-lymphocyte ratio (NLR) and tumor grade in patients with newly diagnosed NMIBC.
Methodology: This prospective cross-sectional analytical study was conducted at a tertiary care center from July 2025 to December 2025. Adult patients (≥18 years) with histologically confirmed NMIBC undergoing transurethral resection of bladder tumor (TURBT) were included. Patients with muscle-invasive disease, prior bladder cancer treatment, active infections, autoimmune disorders, or other confounding conditions were excluded. Preoperative complete blood counts were used to calculate NLR. Tumor characteristics and histopathological grading were recorded. Statistical analysis was performed using SPSS version 26.0, with p < 0.05 considered statistically significant.
Results: A total of 71 patients were included, with a mean age of 56.3 ± 12.7 years. Low-grade NMIBC was observed in 53 patients (74.6%), while 18 patients (25.4%) had high-grade tumors. Median preoperative NLR was significantly higher in the high-grade group compared to the low-grade group [3.7 (IQR 3.2–4.1) vs 2.4 (IQR 2.0–2.8); p < 0.001]. An NLR cutoff value of 3.0 demonstrated acceptable discriminatory ability for predicting high-grade NMIBC (AUC = 0.76; 95% CI: 0.65–0.87; p < 0.01).
Conclusion: Elevated preoperative neutrophil-to-lymphocyte ratio (NLR ≥3) is significantly associated with high-grade NMIBC and may serve as a simple, cost-effective biomarker for identifying patients with aggressive disease at diagnosis.
Keywords: Biomarkers, Lymphocyte, Neutrophil, Transitional cell carcinoma, Urinary bladder carcinoma.
References
Babjuk M, Burger M, Comperat EM. European Association of Urology Guidelines on Non-Muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma In Situ) – 2022 Update. Eur Urol. 2022;81(1):75–94. https://doi.org/10.1016/j.eururo.2021.05.041
Witjes JA, Babjuk M, Bellmunt J. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur Urol. 2021;79(1):82–104. https://doi.org/10.1016/j.eururo.2020.03.055
van den Bosch S, Witjes JA. Long-term cancer-specific survival in patients with high-risk, non–muscle-invasive bladder cancer and tumor progression: A systematic review. Eur Urol. 2021;79(6):822–832. https://doi.org/10.1016/j.eururo.2021.01.019
Fernández-Gómez J, Solsona E, Unda M. The CUETO scoring model for predicting non–muscle-invasive bladder cancer recurrence and progression in patients treated with Bacillus Calmette-Guérin. Eur Urol Focus. 2020;6(4):709–715. https://doi.org/10.1016/j.euf.2019.05.007
Zhou J, Peng Z, Liu X. Prognostic value of neutrophil-to-lymphocyte ratio in patients undergoing radical cystectomy for bladder cancer: A systematic review and meta-analysis. Front Oncol. 2020;10:1657. https://doi.org/10.3389/fonc.2020.01657
Wang N, Ren C, Wen Y. Preoperative neutrophil-to-lymphocyte ratio predicts survival in patients with bladder cancer treated with radical cystectomy: A meta-analysis. Cancer Biomark. 2019;25(4):411–420. https://doi.org/10.3233/CBM-181183
Xiao J, Zhang X, Huang Z. Prognostic role of neutrophil-to-lymphocyte ratio in bladder cancer: A meta-analysis. BMC Cancer. 2021;21(1):1211. https://doi.org/10.1186/s12885-021-08839-9
Shimizu T, Kawada K, Takahashi M. Preoperative neutrophil-to-lymphocyte ratio as a predictor of tumor aggressiveness and recurrence in non-muscle invasive bladder cancer. Int J Urol. 2022;29(3):272–279. https://doi.org/10.1111/iju.14788
Brierley J, Giuliani M, O’Sullivan B, Rous B, Van Eycken E, editors. TNM Classification of Malignant Tumours. 9th ed. Hoboken, NJ: Wiley; 2025.
Kim WT, Kim WJ. The role of neutrophil-to-lymphocyte ratio as a biomarker for predicting recurrence and progression in non–muscle invasive bladder cancer: A systematic review. World J Urol. 2020;38(6):1521–1530. https://doi.org/10.1007/s00345-019-02969-4
Liu H, Wang X, Li Y. Neutrophil-to-lymphocyte ratio as a prognostic factor for tumor aggressiveness and recurrence in non-muscle invasive bladder cancer. J Cancer Res Clin Oncol. 2022;148(3):765–773. https://doi.org/10.1007/s00432-021-03851-x
Kim HJ, Park J, Lee S. Neutrophil-to-lymphocyte ratio as a predictor of recurrence and progression in NMIBC treated with BCG therapy. World J Urol. 2021;39(7):2549–2556. https://doi.org/10.1007/s00345-020-03487-3
Zhang Y, Chen J, Wang L. Prognostic value of neutrophil-to-lymphocyte ratio in bladder cancer: A meta-analysis. Cancer Med. 2023;12(4):5238–5248. https://doi.org/10.1002/cam4.5567
Huang J, He L, Guo Q. Elevated neutrophil-to-lymphocyte ratio predicts high-grade pathology and early recurrence in NMIBC patients. BMC Urol. 2020;20:108. https://doi.org/10.1186/s12894-020-00731-x
Vartolomei MD, Porav-Hodade D, Ferro M. Prognostic role of neutrophil-to-lymphocyte ratio (NLR) in non-muscle invasive bladder cancer: A systematic review and meta-analysis. Urol Oncol. 2018;36(9):389–399. https://doi.org/10.1016/j.urolonc.2018.05.018
Ferro M, Lucarelli G, Bruzzese D. Neutrophil-to-lymphocyte ratio predicts recurrence in patients with T1G3 non-muscle invasive bladder cancer treated with BCG. Oncotarget. 2017;8(1):1063–1070. https://doi.org/10.18632/oncotarget.13000
Getzler I, Bahouth Z, Nativ O, Rubinstein J, Halachmi S. Neutrophil-to-lymphocyte ratio predicts disease progression in patients with non–muscle-invasive bladder cancer. Urol Oncol. 2018;36(4):159.e15–159.e19. https://doi.org/10.1016/j.urolonc.2017.11.001
Lee S, Kim HJ, Park J. Neutrophil-to-lymphocyte ratio as a prognostic marker in NMIBC patients undergoing intravesical BCG therapy: A prospective study. Diagnostics (Basel). 2023;13(19):3114. https://doi.org/10.3390/diagnostics13193114
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