The Effect of Transurethral Resection and BCG Therapy on Cytokine Levels in Non-Muscle Invasive Bladder Cancer

The Effect of Transurethral Resection and BCG Therapy on Cytokine Levels in Non-Muscle Invasive Bladder Cancer

Objective: The present study investigated the effect of treatment on interleukin (IL)-1, IL-6, IL-8, and neopterin levels in patients with non-muscle invasive bladder cancer (NMIBC). Materials and Methods: Thirty patients with NMIBC and 30 age-matched controls were included in the study. Preoperative, postoperative first control [at two weeks after second transurethral resection of bladder tumor (TURBT)] and the second control (at the end of intravesical immunotherapy) blood samples were analyzed using ELISA to determine IL-1, IL-6, IL-8, and neopterin levels. The mean cytokine levels of the patients were statistically compared and comparing the patients’ and controls’ levels. Results: There were no statistically significant differences between the mean IL-1, IL-6, IL-8, and neopterin levels of the patient and control groups before initial TURBT. In the patient group, there were no statistically significant differences in the IL-6 and IL-8 levels after both TURBT and intravesical Bacillus Calmette-Guérin (BCG) therapy. The mean of preoperative IL-1 and neopterin levels significantly decreased after TURBT (p

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  • 1. Babjuk M, Burger M, Compérat EM, Gontero P, Mostafid AH, Palou J, van Rhijn BWG, Rouprêt M, Shariat SF, Sylvester R, Zigeuner R, Capoun O, Cohen D, Escrig JLD, Hernández V, Peyronnet B, Seisen T, Soukup V. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update. Eur Urol 2019;76:639-657.
  • 2. Malmström PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, Solsona E, Di Stasi SM, Witjes JA. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer. Eur Urol 2009;56:247-256.
  • 3. Han RF, Pan JG. Can intravesical bacillus Calmette-Guérin reduce recurrence in patients with superficial bladder cancer? A meta-analysis of randomized trials. Urology 2006;67:1216-1223.
  • 4. Böhle A, Bock PR. Intravesical bacille Calmette-Guérin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology 2004;63:682-686; discussion 686-687.
  • 5. Sylvester RJ, van der MEIJDEN AP, Lamm DL. Intravesical bacillus Calmette- Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 2002;168:1964-1970.
  • 6. Temeltaş G, Kosova F, Üçer O, Müezzinoğlu T, Arı Z. Effects of Treatment on Angiogenic (Vascular Endothelial Growth Factor-2 and Matrix Metalloproteinase-2) and Antiangiogenic (Endostatin and Thrombospondin-1) Factors in Non-muscle Invasive Bladder Carcinoma. J Urol Surg 2017;4:71-75.
  • 7. Qu K, Gu J, Ye Y, Williams SB, Dinney CP, Wu X, Kamat A. High baseline levels of interleukin-8 in leukocytes and urine predict tumor recurrence in nonmuscle invasive bladder cancer patients receiving bacillus Calmette-Guerin therapy: A long-term survival analysis. Oncoimmunology 2017;6:e1265719.
  • 8. Böhle A, Brandau S. Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer. J Urol 2003;170:964-969.
  • 9. Takeuchi A, Dejima T, Yamada H, Shibata K, Nakamura R, Eto M, Nakatani T, Naito S, Yoshikai Y. IL-17 production by γδ T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guérin treatment against bladder cancer. Eur J Immunol 2011;41:246-251.
  • 10. Ma Y, Ren Y, Dai ZJ, Wu CJ, Ji YH, Xu J. IL-6, IL-8 and TNF-α levels correlate with disease stage in breast cancer patients. Adv Clin Exp Med 2017;26:421- 426.
  • 11. Mantovani A, Barajon I, Garlanda C. IL-1 and IL-1 regulatory pathways in cancer progression and therapy. Immunol Rev 2018;281:57-61.
  • 12. Isci Bostanci E, Ugras Dikmen A, Girgin G, Gungor T, Baydar T, Nuri Danisman A. A New Diagnostic and Prognostic Marker in Endometrial Cancer: Neopterin. Int J Gynecol Cancer 2017;27:754-758.
  • 13. De Boer EC, De Jong WH, Steerenberg PA, Aarden LA, Tetteroo E, De Groot ER, Van der Meijden AP, Vegt PD, Debruyne FM, Ruitenberg EJ. Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette-Guérin in superficial bladder cancer. Cancer Immunol Immunother 1992;34:306-312.
  • 14. Böhle A, Nowc C, Ulmer AJ, Musehold J, Gerdes J, Hofstetter AG, Flad HD. Detection of urinary TNF, IL 1, and IL 2 after local BCG immunotherapy for bladder carcinoma. Cytokine 1990;2:175-181.
  • 15. Mack D, Gomahr A, Herold M, Frick J. Neopterin as a monitoring parameter for treatment with BCG in superficial bladder cancer. Eur J Cancer 1995;31A:1025-1026.
  • 16. Hwang EC, Jung SI, Lee HJ, Lee JJ, Kwon DD. Generation of potent cytotoxic T lymphocytes against in male patients with non-muscle invasive bladder cancer by dendritic cells loaded with dying T24 bladder cancer cells. Int Braz J Urol 2017;43:615-627.
  • 17. Chen MF, Lin PY, Wu CF, Chen WC, Wu CT. IL-6 expression regulates tumorigenicity and correlates with prognosis in bladder cancer. PLoS One 2013;8:e61901.
  • 18. Cai T, Nesi G, Mazzoli S, Meacci F, Tinacci G, Luciani LG, Ficarra V, Malossini G, Bartoletti R. Prediction of response to bacillus Calmette-Guérin treatment in non-muscle invasive bladder cancer patients through interleukin-6 and interleukin-10 ratio. Exp Ther Med 2012;4:459-464.
  • 19. Kamat AM, Briggman J, Urbauer DL, Svatek R, Nogueras González GM, Anderson R, Grossman HB, Prat F, Dinney CP. Cytokine Panel for Response to Intravesical Therapy (CyPRIT): Nomogram of Changes in Urinary Cytokine Levels Predicts Patient Response to Bacillus Calmette-Guérin. Eur Urol 2016;69:197-200.
  • 20. Kumari N, Agrawal U, Mishra AK, Kumar A, Vasudeva P, Mohanty NK, Saxena S. Predictive role of serum and urinary cytokines in invasion and recurrence of bladder cancer. Tumour Biol 2017;39:1010428317697552.