Urinary cytokines in patients treated with intravesical mitomycin-C with and without hyperthermia

World J Urol. 2015 Oct;33(10):1411-7. doi: 10.1007/s00345-014-1458-3. Epub 2014 Dec 10.


Objectives: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders.

Methods: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex(®)-analysis.

Results: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders.

Conclusion: MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.

Keywords: Bladder cancer; Bladder instillation; Chemotherapy; Cytokines; Induced hyperthermia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravesical
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / administration & dosage
  • Biomarkers, Tumor / urine
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / therapy*
  • Cytokines / urine*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Hyperthermia, Induced / methods*
  • Instillation, Drug
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage*
  • Retrospective Studies
  • Treatment Outcome
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*


  • Antibiotics, Antineoplastic
  • Biomarkers, Tumor
  • Cytokines
  • Mitomycin