ASSESSMENT OF URINARY BIOMARKERS FOR EARLY BLADDER CANCER DIAGNOSIS A CROSS SECTIONAL STUDY
Main Article Content
Keywords
Bladder cancer, urinary biomarkers, early detection, non-invasive diagnosis
Abstract
Background
Bladder cancer is a major health problem worldwide with the disease presenting usually at an advanced stage because of the challenges associated with the current practice of diagnosing diseases such as bladder cancer through cystoscopy and cytology. The use of urinary biomarkers provides an efficient method to diagnose a disease at early stage and with less costs than invasive methods and so has potential to favorably influence patient prognosis.
Objectives
To determine the performance of urinary biomarkers in diagnosing the early-stage bladder cancer and to compare the results with the current diagnostic measures.
Study design: A Cross Sectional study
Place and Duration of study. March 2021 and Sep 2021 in a Urology MTI BKMC/MMC Mardan Pakistan
Methods
This case-control study used 100 patients with hematuria or risk factors for bladder cancer. Std 5% urines were examined for biomarkers such as NMP22, UroVysion FISH, and cytokeratin fragments. Data analysis was done using the statistical package for the social sciences – SPSS version twenty-four [SPSS Inc., Chicago, IL, USA]. For numerical data, continuous variables were described using mean ± SD, and for nominal data using percentages.
Results
Among 100 patients (mean age: 62.Age was 5 ± 8.2 years with 65% males and 55% having gross haematuria; overall urinary biomarkers had a combined sensitivity of 85% and specificity of 78% for early BlCA (p < 0.05). The detection of NMP22 had the highest sensitivity level at 88% while UroVysion FISH had the highest specificity level of 82%. Our study further revealed that biomarkers were significantly more sensitive than cytology (p = .03.
Conclusion
Urinary biomarkers provide a high diagnostic sensitivity and specificity thus providing an efficient, less invasive mode of diagnosing early stage bladder cancer. Applying these biomarkers into common models of practice care could help to bring early diagnosis, better decrease invasive testing and better outcomes to the patient.
References
2. Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 70(1), 7-30. https://doi.org/10.3322/caac.21590
3. Kamat, A. M., Hegarty, P. K., Gee, J. R., Clark, P. E., Svatek, R. S., Hegarty, N., ... & Boorjian, S. A. (2016). ICUD-EAU International Consultation on Bladder Cancer 2012: Screening, diagnosis, and molecular markers. European Urology, 63(1), 4-15. https://doi.org/10.1016/j.eururo.2012.09.054
4. Babjuk, M., Burger, M., Compérat, E. M., Gontero, P., Mostafid, A. H., Palou, J., ... & Shariat, S. F. (2019). European Association of Urology Guidelines on non–muscle-invasive bladder cancer (TaT1 and CIS). European Urology, 76(5), 639-657. https://doi.org/10.1016/j.eururo.2019.08.016
5. Lokeshwar, V. B., Habuchi, T., Grossman, H. B., Murphy, W. M., Hautmann, S. H., Hemstreet, G. P., ... & Fradet, Y. (2005). Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers. Urology, 66(6), 35-63. https://doi.org/10.1016/j.urology.2005.07.017
6. Lotan, Y., & Roehrborn, C. G. (2003). Sensitivity and specificity of commonly available bladder tumor markers versus cytology: Results of a comprehensive literature review and meta-analyses. Urology, 61(1), 109-118. https://doi.org/10.1016/S0090-4295(02)02198-2
7. Grossman, H. B., Messing, E., Soloway, M., Tomera, K., Katz, G., Berger, Y., & Shen, Y. (2005). Detection of bladder cancer using a point-of-care proteomic assay. JAMA, 293(7), 810-816. https://doi.org/10.1001/jama.293.7.810
8. Halling, K. C., King, W., Sokolova, I. A., Karnes, R. J., Meyer, R. G., Powell, E. L., ... & Sebo, T. J. (2000). A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma. The Journal of Urology, 164(5), 1768-1775. https://doi.org/10.1016/S0022-5347(05)67055-0
9. Konety, B. R., Nguyen, T. S., Dhir, R., Day, R. S., Becich, M. J., Stadler, W. M., & Getzenberg, R. H. (2000). Detection of bladder cancer using a novel nuclear matrix protein, BLCA-4. Clinical Cancer Research, 6(7), 2618-2625.
10. Shariat, S. F., Marberger, M. J., Lotan, Y., & Sánchez-Carbayo, M. (2008). Early detection of bladder cancer: Microscopic and molecular markers. Expert Review of Anticancer Therapy, 8(7), 1131-1142. https://doi.org/10.1586/14737140.8.7.1131
11. Miyanaga, N., Akaza, H., Okamura, T., Ohtani, M., Uchida, T., Koiso, K., ... & Soloway, M. S. (1999). Urinary NMP22 and bladder cancer: A clinical evaluation. Japanese Journal of Clinical Oncology, 29(12), 604-606. https://doi.org/10.1093/jjco/29.12.604
12. Chou, R., Gore, J. L., Buckley, D., Fu, R., Gustafson, K., Griffin, J. C., & Grusing, S. (2015). Urinary biomarkers for diagnosis of bladder cancer: A systematic review and meta-analysis. Annals of Internal Medicine, 163(12), 922-931. https://doi.org/10.7326/M15-0997
13. Witjes, J. A., Morote, J., Cornel, E. B., Gakis, G., van Valenberg, F. J. P., de Jong, F. C., ... & de Reijke, T. M. (2018). Performance of the Bladder EpiCheck™ methylation test for patients under surveillance for non–muscle-invasive bladder cancer: Results of a multicenter, prospective, blinded clinical trial. European Urology Oncology, 1(4), 307-313. https://doi.org/10.1016/j.euo.2018.02.002
14. Yafi, F. A., Brimo, F., Steinberg, J., Aprikian, A. G., Tanguay, S., & Kassouf, W. (2015). Prospective analysis of sensitivity and specificity of urinary cytology and other urinary biomarkers for bladder cancer. Urologic Oncology: Seminars and Original Investigations, 33(2), 66-e25. https://doi.org/10.1016/j.urolonc.2014.06.001
15. Green, D. A., Rink, M., Matin, S. F., Stenzl, A., Rouprêt, M., & Babjuk, M. (2013). Urothelial carcinoma of the bladder and the upper tract: Disparate twins. The Journal of Urology, 189(4), 1214-1221. https://doi.org/10.1016/j.juro.2012.12.030
16. O'Sullivan, P., Sharples, K., Dalphin, M., Davidson, P., Gilling, P., Cambridge, L., ... & Harris, M. (2012). A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria. The Journal of Urology, 188(3), 741-747. https://doi.org/10.1016/j.juro.2012.05.009
17. Grossman, H. B., Soloway, M., Messing, E., Katz, G., Stein, B., Kassabian, V., ... & Shen, Y. (2006). Detection of bladder cancer using a point-of-care proteomic assay. JAMA, 295(4), 299-305. https://doi.org/10.1001/jama.295.3.299
18. Getzenberg, R. H. (1996). Nuclear matrix and the regulation of gene expression: Tissue specificity. Journal of Cellular Biochemistry, 62(2), 145-148. https://doi.org/10.1002/(SICI)1097-4644(19960801)62:2%3C145::AID-JCB2%3E3.0.CO;2-7
19. Svatek, R. S., Herman, M. P., Lotan, Y., Karakiewicz, P. I., Shariat, S. F., & Dinney, C. P. (2009). The use of urinary markers in surveillance of patients with high-risk non-muscle-invasive bladder cancer: Bladder tumour markers beyond cytology. Cancer, 115(12), 2641-2650. https://doi.org/10.1002/cncr.24268
20. Babjuk, M., Böhle, A., Burger, M., Capoun, O., Cohen, D., Compérat, E. M., ... & Zigeuner, R. (2017). EAU Guidelines on non–muscle-invasive bladder cancer (TaT1 and CIS). European Urology, 71(3), 447-461. https://doi.org/10.1016/j.eururo.2016.12.038
21. van Rhijn, B. W., van der Poel, H. G., & van der Kwast, T. H. (2005). Urine markers for bladder cancer surveillance: A systematic review. European Urology, 47(6), 736-748. https://doi.org/10.1016/j.eururo.2005.01.014