Cancer Immunology, Immunotherapy

, Volume 52, Issue 8, pp 481–486

Urinary interleukin-2 may predict clinical outcome of intravesical bacillus Calmette-Guérin immunotherapy for carcinoma in situ of the bladder

  • Etsuya Watanabe
  • Hideyasu Matsuyama
  • Kenji Matsuda
  • Chietaka Ohmi
  • Yasuhide Tei
  • Satoru Yoshihiro
  • Yasukazu Ohmoto
  • Katsusuke Naito
Original Article

DOI: 10.1007/s00262-003-0384-9

Cite this article as:
Watanabe, E., Matsuyama, H., Matsuda, K. et al. Cancer Immunol Immunother (2003) 52: 481. doi:10.1007/s00262-003-0384-9

Abstract

Purpose

The mechanism by which bacillus Calmette-Guérin (BCG) mediates antitumor activity has not been clearly established. Specific cytokines in the urine after BCG intravesical instillation therapy may serve as a prognostic factor of treatment response. In this study, various urinary cytokines such as interleukin-1β (IL-1β), IL-2, IL-6, IL-8. IL-10, IL-12, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were measured.

Materials and methods

In total 20 patients were treated with BCG intravesical instillation therapy for carcinoma in situ of the bladder . At the completion of the first and eighth instillations, spontaneously voided urine specimens were collected before BCG instillation, every 2 h until 12 h, and thereafter until 24 h. All specimens were ultrafiltrated using an ADVANTEC UK-10 membrane. The cytokines were measured using ELISA and RIA techniques.

Results

Significantly higher levels of IL-2, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were detected in the eighth instillation as compared to the first instillation (p<0.001). After BCG intravesical instillation therapy, treatment failure occurred in 6 of the 20 patients (30%), including primary failure (persistence of CIS) in 3, and de novo failure (tumor recurrence) in 3 with a median follow-up of 46.9 months. Significantly higher production of IL-2, IL-6, IL-8, IL-10, and TNF-α was observed in the responder group than in the non-responder group (p<0.05). Multivariate analysis revealed IL-2 as an independent prognostic cytokine of responder status.

Conclusions

This study indicates that urinary IL-2 at the eighth instillation of BCG may serve as a valuable prognostic factor of treatment efficacy as well as tumor recurrence after treatment.

Keywords

BCGCytokinesBladder cancerIL-2Prognosis

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Etsuya Watanabe
    • 1
  • Hideyasu Matsuyama
    • 1
  • Kenji Matsuda
    • 1
  • Chietaka Ohmi
    • 1
  • Yasuhide Tei
    • 1
  • Satoru Yoshihiro
    • 1
  • Yasukazu Ohmoto
    • 2
  • Katsusuke Naito
    • 1
  1. 1.Department of UrologyYamaguchi University School of MedicineYamaguchiJapan
  2. 2.Cellular Technology InstitutesOtsuka Pharmaceutical Co.TokushimaJapan