Association between creatinine-to-hemoglobin ratio and advanced disease features in bladder cancer

Abstract

Introduction: Bladder cancer (BC) is frequently marked by high recurrence and progression rates, making close follow-up essential. Cystoscopy remains the standard method for surveillance; however, it is invasive, costly, and uncomfortable for patients. Given these limitations, there is increasing interest in identifying minimally invasive biomarkers to support clinical management.

Objectives: This study aims to assess the potential prognostic role of the creatinine-to-hemoglobin ratio (CHR) in individuals with BC.

Methods: A retrospective study was performed on 148 patients with BC treated at the Urology Department of Mureș Clinical County Hospital. Patients’ clinical, pathological, and laboratory data were collected. CHR was calculated from routine blood test parameters. The association between CHR and tumor-related parameters was assessed using statistical testing, primarily employing non-parametric methods and Spearman’s rank correlation analysis.

Results: Elevated CHR values were significantly associated with more advanced tumor stages (median CHR: 0.10 in pT2 vs. 0.07 in pTa; p < 0.001), lower hematocrit levels, and higher tumor grades. CHR demonstrated weak but statistically significant correlations with tumor stage (r = 0.274), grade (r = 0.274), and patient age (r = 0.16). No significant association was observed between CHR and tumor size.

Conclusion: As a marker derived from routine laboratory tests, CHR may provide useful information for the assessment of BC patients, particularly those with advanced disease features. CHR appears to be associated with adverse pathological characteristics and may serve as a supportive indicator of disease burden. These preliminary findings emphasize the need for further prospective studies to determine whether CHR could be integrated into existing risk assessment tools and follow-up strategies.

Keywords

Non-muscle-invasive bladder cancer / Muscle-invasive bladder cancer / Blood-based biomarkers / Risk stratification / Creatinine-to-hemoglobin ratio

References

[1] Dyrskjøt L, Hansel DE, Efstathiou JA, et al. Bladder cancer. Nat Rev Dis Primers. 2023; 9(1):58. doi: 10.1038/s41572-023-00468-9

[2] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. doi: 10.3322/caac.21660

[3] Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. Eur Urol. 2017; 71(1):96-108. doi: 10.1016/j.eururo.2016.06.010

[4] Tran L, Xiao JF, Agarwal N, Duex JE, Theodorescu D. Advances in bladder cancer biology and therapy. Nat Rev Cancer. 2021; 21(2):104-121. doi: 10.1038/s41568-020-00313-1

[5] Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. Epidemiology of Bladder Cancer. Med Sci. 2020; 8(1):15. doi: 10.3390/medsci8010015

[6] Russell B, Liedberg F, Hagberg O, et al. Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer. Scand J Urol. 2022; 56(1):27-33. doi: 10.1080/21681805.2021.2002399

[7] Tătar AC, Loghin A, Nechifor-Boilă A, et al. Urothelial Bladder Carcinoma in Young and Elderly Patients: Pathological Insights and Age-Related Variations. Cancers. 2025; 17(5):5. doi: 10.3390/cancers17050845

[8] Cochetti G, Rossi de Vermandois JA, Maulà V, et al. Diagnostic performance of the Bladder EpiCheck methylation test and photodynamic diagnosis-guided cystoscopy in the surveillance of high-risk non-muscle invasive bladder cancer: A single centre, prospective, blinded clinical trial. Urol Oncol. 2022; 40(3):105.e11-105.e18. doi: 10.1016/j.urolonc.2021.11.001

[9] Holzbeierlein JM, Bixler BR, Buckley DI, et al. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/ SUO Guideline: 2024 Amendment. J Urol. 2024; 211(4):533. doi: 10.1097/JU.0000000000003846

[10] Kausch I, Sommerauer M, Montorsi F, et al. Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urol. 2010; 57(4):595-606. doi: 10.1016/j.eururo.2009.11.041

[11] Sylvester RJ, van der Meijden APM, Oosterlinck W, 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(3):466-465; discussion 475-477. doi: 10.1016/j.eururo.2005.12.031

[12] Witjes JA. Follow-up in non-muscle invasive bladder cancer: facts and future. World J Urol. 2021; 39(11):4047-4053. doi: 10.1007/s00345-020-03569-2

[13] Wolfs JRE, Hermans TJN, Koldewijn EL, van de Kerkhof D. Novel urinary biomarkers ADXBLADDER and bladder EpiCheck for diagnostics of bladder cancer: A review. Urol Oncol. 2021; 39(3):161-170. doi: 10.1016/j.urolonc.2020.11.014

[14] Chen H, Wu X, Wen Z, Zhu Y, Liao L, Yang J. The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer. Arch Esp Urol. 2022; 75(5):467-471. doi: 10.56434/j.arch.esp.urol.20227505.68

[15] Huang J, Lin L, Mao D, Hua R, Guan F. Prognostic value of neutrophil-to-lymphocyte ratio in patients with non-muscle-invasive bladder cancer with intravesical Bacillus Calmette-Guérin immunotherapy: a systematic review and meta-analysis. Front Immunol. 2024; 15:1464635. doi: 10.3389/fimmu.2024.1464635

[16] Mjaess G, Chebel R, Karam A, et al. Prognostic role of neutrophil-to-lymphocyte ratio (NLR) in urological tumors: an umbrella review of evidence from systematic reviews and meta-analyses. Acta Oncol. 2021; 60(6):704-713. doi: 10.1080/0284186X.2021.1886323

[17] Wang X, Zhang S, Sun Y, Cai L, Zhang J. The prognostic significance of preoperative platelet-to-lymphocyte ratio and interleukin-6 level in non-muscle invasive bladder cancer. Int J Biol Markers. 2024; 39(3):255-264. doi: 10.1177/03936155241261719

[18] Mártha O, Balan D, Porav-Hodade D, et al. The role of neutrophil to lymphocyte ratio in patients with pTa non-muscle invasive bladder cancer. Rev Romana Med Lab. 2020; 28(1):29-38. doi: 10.2478/rrlm-2020-0001

[19] Wu R, Li D, Zhang F, Bai Y, Wang X, Han P. Prognostic Value of Platelet-to-Lymphocyte Ratio in Non-Muscle Invasive Bladder Cancer Patients: Intravesical Bacillus Calmette- Guerin Treatment After Transurethral Resection of Bladder Tumor. Front Surg. 2022; 9:907485. doi: 10.3389/fsurg.2022.907485

[20] Ivanić D, Đug H, Jagodić S, Delibegović S. Preoperative neutrophil-to-lymphocyte ratio (NLR) value as a predictor of recurrence of non-muscle-invasive bladder cancer. Int Urol Nephrol. 2025; 57(4):1143-1149. doi: 10.1007/s11255-024-04297-x

[21] Li J, Cao D, Huang Y, et al. The Prognostic and Clinicopathological Significance of Systemic Immune- Inflammation Index in Bladder Cancer. Front Immunol. 2022; 13:865643. doi: 10.3389/fimmu.2022.865643

[22] Hosten AO. BUN and Creatinine. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Butterworths; 1990. Available from: Last accessed on April 18, 2025].

[23] Hamano I, Hatakeyama S, Iwamurau H, et al. Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer. Oncotarget. 2017; 8(37):61404-61414. doi: 10.18632/oncotarget.18248

[24] Meagher MF, Cerrato C, Nguyen MV, et al. Elevated creatinine-to-hemoglobin ratio is a novel preoperative marker for worsened survival outcomes in upper tract urothelial carcinoma: analysis from the ROBUUST registry. Minerva Urol Nephrol. 2025; 77(6):795-802. doi: 10.23736/S2724-6051.25.05498-9

[25] van Rhijn BWG, Hentschel AE, Bründl J, et al. Prognostic Value of the WHO1973 and WHO2004/2016 Classification Systems for Grade in Primary Ta/T1 Non-muscle-invasive Bladder Cancer: A Multicenter European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel Study. Eur Urol Oncol. 2021; 4(2):182-191. doi: 10.1016/j.euo.2020.12.002

[26] Badireddy M, Baradhi KM. Chronic Anemia. In: StatPearls. StatPearls Publishing; 2025. Available from: http://www.ncbi.nlm.nih.gov/books/NBK534803/ [Last accessed on April 18, 2025].

[27] EAU Guidelines on Non-muscle-invasive Bladder Cancer - Uroweb. Available from: https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer [Last accessed on April 18, 2025].

[28] Soukup V, Babjuk M, Bellmunt J, et al. Follow-up after surgical treatment of bladder cancer: a critical analysis of the literature. Eur Urol. 2012; 62(2):290-302. doi: 10.1016/j.eururo.2012.05.008

[29] Mariappan P, Project Collaborators. The Scottish Bladder Cancer Quality Performance Indicators Influencing Outcomes, Prognosis, and Surveillance (Scot BC Quality OPS) Clinical Project. Eur Urol Focus. 2021; 7(5):905-908. doi: 10.1016/j.euf.2021.07.011

[30] Soorojebally Y, Neuzillet Y, Roumiguié M, et al. Urinary biomarkers for bladder cancer diagnosis and NMIBC follow-up: a systematic review. World J Urol. 2023; 41(2):345-359. doi: 10.1007/s00345-022-04253-3

[31] Ohlmann CH, Albers P, Boehm K, et al. Follow-up of urological tumor treatment. Urologe A. 2015; 54(9):1223-1233. doi: 10.1007/s00120-015-3936-7

[32] van Osch FHM, Nekeman D, Aaronson NK, et al. Patients choose certainty over burden in bladder cancer surveillance. World J Urol. 2019; 37(12):2747-2753. doi: 10.1007/s00345-019-02728-4

[33] Meagher MF, Autorino R, Mehrazin R, et al. A0292 - Elevated hemoglobin: Creatinine ratio is a novel preoperative marker for worsened survival outcomes in upper tract urothelial carcinoma: Analysis from the robuust registry. Eur Urol. 2022; 81:S452-S453. doi: 10.1016/S0302-2838(22)00379-7

[34] Matuszczak M, Salagierski M. Diagnostic and Prognostic Potential of Biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in Bladder Cancers. Int J Mol Sci. 2020; 21(9). doi: 10.3390/ijms21093360