Urinary interleukin-2 may predict clinical outcome of intravesical bacillus Calmette-Guérin immunotherapy for carcinoma in situ of the bladder
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- Watanabe, E., Matsuyama, H., Matsuda, K. et al. Cancer Immunol Immunother (2003) 52: 481. doi:10.1007/s00262-003-0384-9
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.
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.
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.