Urinary interleukin-2 may predict clinical outcome of intravesical bacillus Calmette-Guérin immunotherapy for carcinoma in situ of the bladder.
OBJECTIVE
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-1beta (IL-1beta), IL-2, IL-6, IL-8. IL-10, IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured.


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-gamma, and TNF-alpha 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-alpha 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.
Watanabe
Etsuya
E
Department of Urology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi Ube, 755-8505, Yamaguchi, Japan.
Matsuyama
Hideyasu
H
Matsuda
Kenji
K
Ohmi
Chietaka
C
Tei
Yasuhide
Y
Yoshihiro
Satoru
S
Ohmoto
Yasukazu
Y
Naito
Katsusuke
K
D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000652:urine; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000652:urine; D016022:Case-Control Studies; D016207:Cytokines / Q000652:urine; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000628:therapy / Q000652:urine; D009367:Neoplasm Staging; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000652:urine
D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha