Novel Hematologic Markers for Risk Stratification in Bladder Cancer Patients Receiving BCG Treatment
Abstract
Objective: In order to evaluate the predictive role of novel hematologic markers in recurrence and progression among non-muscle invasive bladder cancer (NMIBC) patients undergoing intravesical BCG therapy.
Material and Methods: A total of 182 patients diagnosed with NMIBC and treated with transurethral resection of bladder tumor (TUR-BT) followed by BCG therapy were included. Patients were stratified into intermediate-, high- and very high-risk groups per the EAU 2024 guidelines. Preoperative hematologic parameters were recorded. In addition, CLR, CAR, and IBI were calculated. Recurrence and progression were assessed through follow-up cystoscopies. ROC curve analysis was used to determine the predictive value of the biomarkers.
Results: Recurrence and progression occurred in 15% and 8% of patients, respectively. Multifocal tumors showed a notable association with recurrence (p = 0.006), and carcinoma in situ (CIS) predicted progression (p < 0.001). CAR (AUC = 0.695, p = 0.013) and CLR (AUC = 0.660, p = 0.040) significantly predicted progression. IBI was a strong predictor in the very high-risk group (AUC = 0.920, p < 0.001).
Conclusion: CLR, CAR, and IBI are promising markers for identifying patients at higher risk of progression during BCG therapy. IBI shows strong prognostic utility in very high-risk NMIBC patients. Further prospective, multicenter studies are needed for clinical validation.
Keywords
BCG Haematological inflammatory markers Non-muscle invasive bladder cancer Progression Recurrence
Ethical Statement
Haydarpaşa Numune Training and Research Hospital Clinical Research Ethics Committee Date: 29.02.2024 Land No: HNEAH/KAEK-2024/KK/9
Supporting Institution
None.
References
- 1. Babjuk M, Burger M, Comperat EM, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update. Eur Urol. 2019;76(5):639-657. https://doi.org/10.1016/j.eururo.2019.08.016
- 2. Sylvester RJ, Rodriguez O, Hernandez V, et al. European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel. Eur Urol. 2021;79(4):480-488. https://doi.org/10.1016/j.eururo.2020.12.033
- 3. Comperat EM, Burger M, Gontero P, et al. Grading of Urothelial Carcinoma and The New “World Health Organisation Classification of Tumours of the Urinary System and Male Genital Organs 2016”. Eur Urol Focus. 2019;5(3):457-466. https://doi.org/10.1016/j.euf.2018.01.003
- 4. Mbeutcha A, Shariat SF, Rieken M, et al. Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer. Urol Oncol. 2016;34(11):e17-e24. https://doi.org/10.1016/j.urolonc.2016.05.013
- 5. Vartolomei MD, Porav-Hodade D, Ferro M, et al. Prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) in patients with non-muscle-invasive bladder cancer (NMIBC): A systematic review and meta-analysis. Urol Oncol. 2018;36(9):389-399. https://doi.org/10.1016/j.urolonc.2018.05.014
- 6. Kayar R, Bastug Y, Tokuc E, et al. Pan-immune-inflammation value as a prognostic tool for overall survival and disease-free survival in non-metastatic muscle-invasive bladder cancer. Int Urol Nephrol. 2024;56(2):509-518. https://doi.org/10.1007/s11255-023-03812-w
- 7. Ye K, Xiao M, Li Z, et al. Preoperative systemic inflammation response index is an independent prognostic marker for BCG immunotherapy in patients with non-muscle-invasive bladder cancer. Cancer Med. 2023;12(4):4206-4217. https://doi.org/10.1002/cam4.5284
- 8. Nakamura Y, Shida D, Boku N, et al. Lymphocyte-to-C-Reactive Protein Ratio Is the Most Sensitive Inflammation-Based Prognostic Score in Patients With Unresectable Metastatic Colorectal Cancer. Dis Colon Rectum. 2021;64(11):1331-1341. https://doi.org/10.1097/DCR.0000000000002059
- 9. Xie H, Ruan G, Ge Y, et al. Inflammatory burden as a prognostic biomarker for cancer. Clin Nutr. 2022;41(6):1236-1243. https://doi.org/10.1016/j.clnu.2022.04.019
- 10. Yamagata K, Fukuzawa S, Ishibashi-Kanno N, et al. Association between the C-reactive protein/albumin ratio and prognosis in patients with oral squamous cell carcinoma. Sci Rep. 2021;11(1):5446. https://doi.org/10.1038/s41598-021-83362-2
- 11. Kamat AM, Sylvester RJ, Bohle A, et al. Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group. J Clin Oncol. 2016;34(16):1935-1944. https://doi.org/10.1200/JCO.2015.64.4070
- 12. Chade DC, Shariat SF, Godoy G, et al. Clinical outcomes of primary bladder carcinoma in situ in a contemporary series. J Urol. 2010;184(1):74-80. https://doi.org/10.1016/j.juro.2010.03.032
- 13. Deng-Xiong L, Qing-Xin Y, De-Chao F, et al. Systemic Immune-inflammation Index (SII) During Induction has Higher Predictive Value Than Preoperative SII in Non-muscle-invasive Bladder Cancer Patients Receiving Intravesical Bacillus Calmette -Guerin. Clin Genitourin Cancer. 2023;21(3):e145-e52. https://doi.org/10.1016/j.clgc.2022.11.013
- 14. Wu R, Li D, Zhang F, et al. 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. https://doi.org/10.3389/fsurg.2022.907485
- 15. Okugawa Y, Toiyama Y, Yamamoto A, et al. Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer. Ann Surg. 2020;272(2):342-351. https://doi.org/10.1097/SLA.0000000000003239
- 16. Lu LH, Zhong C, Wei W, et al. Lymphocyte-C-reactive protein ratio as a novel prognostic index in intrahepatic cholangiocarcinoma: A multicentre cohort study. Liver Int. 2021;41(2):378-87. https://doi.org/10.1111/liv.14567
- 17. Cheng CB, Zhang QX, Zhuang LP, et al. Prognostic value of lymphocyte-to-C-reactive protein ratio in patients with gastric cancer after surgery: a multicentre study. Jpn J Clin Oncol. 2020;50(10):1141-9. https://doi.org/10.1093/jjco/hyaa099
- 18. Zhang H, Wang Y, Ni J, et al. Prognostic Value of Lymphocyte-C-Reactive Protein Ratio in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Population-Based Study. Front Oncol. 2021;11:760389. https://doi.org/10.3389/fonc.2021.760389
- 19. Kuroda K, Tasaki S, Horiguchi A, et al. Postoperative C-reactive protein-to-albumin ratio predicts poor prognosis in patients with bladder cancer undergoing radial cystectomy. Mol Clin Oncol. 2021;14(3):54. https://doi.org/10.3892/mco.2021.2216
- 20. Shirakawa T, Makiyama A, Shimokawa M, et al. C-reactive protein/albumin ratio is the most significant inflammatory marker in unresectable pancreatic cancer treated with FOLFIRINOX or gemcitabine plus nab-paclitaxel. Sci Rep. 2023;13(1):8815. https://doi.org/10.1038/s41598-023-34962-7
- 21. Chen H, Wu X, Wen Z, et al. The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer. Arch Esp Urol. 2022;75(5):467-71. https://doi.org/10.56434/j.arch.esp.urol.20227505.68
- 22. de Arruda Camargo GC, Oliveira G, Santos BNS, et al. Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad(R) (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases. Med Oncol. 2024;41(11):287. https://doi.org/10.1007/s12032-024-02533-z
Mesane Kanseri Hastalarında BCG Tedavisi Sırasında Risk Sınıflandırması İçin Yeni Hematolojik Belirteçler
Abstract
Amaç:
İntravezikal BCG tedavisi uygulanan kasa invazive olmayan mesane kanseri (KİOMK) hastalarında, yeni hematolojik belirteçlerin nüks ve progresyon üzerindeki öngörücü rolünü değerlendirmek.
Yöntem:
Transüretral mesane tümörü rezeksiyonu (TUR-MT) sonrası BCG tedavisi uygulanan 182 KİOMK hastası çalışmaya dahil edildi. Hastalar, EAU 2024 kılavuzlarına göre orta, yüksek ve çok yüksek risk gruplarına ayrıldı. Preoperatif hematolojik parametreler kaydedildi; CLO (C-reaktif protein/lenfosit oranı), CAO (C-reaktif protein/albumin oranı) ve İBİ (inflamatuvar belirteç indeksi) hesaplandı. Nüks ve progresyon, takip sistoskopileri ile değerlendirildi. Belirteçlerin öngörücü değerini belirlemek için ROC eğrisi analizi yapıldı.
Bulgular:
Hastaların %15’inde nüks, %8’inde ise progresyon gelişti. Multifokal tümörler ile nüks arasında anlamlı bir ilişki saptandı (p = 0.006); karsinoma in situ (KİS) ise progresyonun anlamlı bir prediktörüydü (p < 0.001). CAO (EAA = 0.695, p = 0.013) ve CLO (EAA = 0.660, p = 0.040) progresyonu öngörmede anlamlı bulundu. İBİ, çok yüksek risk grubunda güçlü bir prediktif değer gösterdi (EAA = 0.920, p < 0.001).
Sonuç:
CLO, CAO ve İBİ, BCG tedavisi süresince progresyon açısından yüksek riskli hastaların belirlenmesinde umut verici biyobelirteçlerdir. İBİ, özellikle çok yüksek riskli KİOMK hastalarında güçlü bir prognostik değere sahiptir. Bu sonuçların klinik geçerliliği için ileriye dönük, çok merkezli çalışmalara ihtiyaç vardır.
References
- 1. Babjuk M, Burger M, Comperat EM, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update. Eur Urol. 2019;76(5):639-657. https://doi.org/10.1016/j.eururo.2019.08.016
- 2. Sylvester RJ, Rodriguez O, Hernandez V, et al. European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel. Eur Urol. 2021;79(4):480-488. https://doi.org/10.1016/j.eururo.2020.12.033
- 3. Comperat EM, Burger M, Gontero P, et al. Grading of Urothelial Carcinoma and The New “World Health Organisation Classification of Tumours of the Urinary System and Male Genital Organs 2016”. Eur Urol Focus. 2019;5(3):457-466. https://doi.org/10.1016/j.euf.2018.01.003
- 4. Mbeutcha A, Shariat SF, Rieken M, et al. Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer. Urol Oncol. 2016;34(11):e17-e24. https://doi.org/10.1016/j.urolonc.2016.05.013
- 5. Vartolomei MD, Porav-Hodade D, Ferro M, et al. Prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) in patients with non-muscle-invasive bladder cancer (NMIBC): A systematic review and meta-analysis. Urol Oncol. 2018;36(9):389-399. https://doi.org/10.1016/j.urolonc.2018.05.014
- 6. Kayar R, Bastug Y, Tokuc E, et al. Pan-immune-inflammation value as a prognostic tool for overall survival and disease-free survival in non-metastatic muscle-invasive bladder cancer. Int Urol Nephrol. 2024;56(2):509-518. https://doi.org/10.1007/s11255-023-03812-w
- 7. Ye K, Xiao M, Li Z, et al. Preoperative systemic inflammation response index is an independent prognostic marker for BCG immunotherapy in patients with non-muscle-invasive bladder cancer. Cancer Med. 2023;12(4):4206-4217. https://doi.org/10.1002/cam4.5284
- 8. Nakamura Y, Shida D, Boku N, et al. Lymphocyte-to-C-Reactive Protein Ratio Is the Most Sensitive Inflammation-Based Prognostic Score in Patients With Unresectable Metastatic Colorectal Cancer. Dis Colon Rectum. 2021;64(11):1331-1341. https://doi.org/10.1097/DCR.0000000000002059
- 9. Xie H, Ruan G, Ge Y, et al. Inflammatory burden as a prognostic biomarker for cancer. Clin Nutr. 2022;41(6):1236-1243. https://doi.org/10.1016/j.clnu.2022.04.019
- 10. Yamagata K, Fukuzawa S, Ishibashi-Kanno N, et al. Association between the C-reactive protein/albumin ratio and prognosis in patients with oral squamous cell carcinoma. Sci Rep. 2021;11(1):5446. https://doi.org/10.1038/s41598-021-83362-2
- 11. Kamat AM, Sylvester RJ, Bohle A, et al. Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group. J Clin Oncol. 2016;34(16):1935-1944. https://doi.org/10.1200/JCO.2015.64.4070
- 12. Chade DC, Shariat SF, Godoy G, et al. Clinical outcomes of primary bladder carcinoma in situ in a contemporary series. J Urol. 2010;184(1):74-80. https://doi.org/10.1016/j.juro.2010.03.032
- 13. Deng-Xiong L, Qing-Xin Y, De-Chao F, et al. Systemic Immune-inflammation Index (SII) During Induction has Higher Predictive Value Than Preoperative SII in Non-muscle-invasive Bladder Cancer Patients Receiving Intravesical Bacillus Calmette -Guerin. Clin Genitourin Cancer. 2023;21(3):e145-e52. https://doi.org/10.1016/j.clgc.2022.11.013
- 14. Wu R, Li D, Zhang F, et al. 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. https://doi.org/10.3389/fsurg.2022.907485
- 15. Okugawa Y, Toiyama Y, Yamamoto A, et al. Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer. Ann Surg. 2020;272(2):342-351. https://doi.org/10.1097/SLA.0000000000003239
- 16. Lu LH, Zhong C, Wei W, et al. Lymphocyte-C-reactive protein ratio as a novel prognostic index in intrahepatic cholangiocarcinoma: A multicentre cohort study. Liver Int. 2021;41(2):378-87. https://doi.org/10.1111/liv.14567
- 17. Cheng CB, Zhang QX, Zhuang LP, et al. Prognostic value of lymphocyte-to-C-reactive protein ratio in patients with gastric cancer after surgery: a multicentre study. Jpn J Clin Oncol. 2020;50(10):1141-9. https://doi.org/10.1093/jjco/hyaa099
- 18. Zhang H, Wang Y, Ni J, et al. Prognostic Value of Lymphocyte-C-Reactive Protein Ratio in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Population-Based Study. Front Oncol. 2021;11:760389. https://doi.org/10.3389/fonc.2021.760389
- 19. Kuroda K, Tasaki S, Horiguchi A, et al. Postoperative C-reactive protein-to-albumin ratio predicts poor prognosis in patients with bladder cancer undergoing radial cystectomy. Mol Clin Oncol. 2021;14(3):54. https://doi.org/10.3892/mco.2021.2216
- 20. Shirakawa T, Makiyama A, Shimokawa M, et al. C-reactive protein/albumin ratio is the most significant inflammatory marker in unresectable pancreatic cancer treated with FOLFIRINOX or gemcitabine plus nab-paclitaxel. Sci Rep. 2023;13(1):8815. https://doi.org/10.1038/s41598-023-34962-7
- 21. Chen H, Wu X, Wen Z, et al. The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer. Arch Esp Urol. 2022;75(5):467-71. https://doi.org/10.56434/j.arch.esp.urol.20227505.68
- 22. de Arruda Camargo GC, Oliveira G, Santos BNS, et al. Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad(R) (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases. Med Oncol. 2024;41(11):287. https://doi.org/10.1007/s12032-024-02533-z
Details
| Primary Language | English |
|---|---|
| Subjects | Urology |
| Journal Section | Research Article |
| Authors | |
| Publication Date | June 29, 2025 |
| Submission Date | May 7, 2025 |
| Acceptance Date | June 11, 2025 |
| Published in Issue | Year 2025 Volume: 20 Issue: 2 |
