Urinary IL-2 assay for monitoring intravesical bacillus Calmette-Guérin response of superficial bladder cancer during induction course and maintenance therapy.

We evaluated the clinical significance of Th1(IL-2)/Th2(IL-10) urinary profiles during a weekly induction course lasting 6 weeks, followed by a weekly maintenance therapy schedule for 3 weeks. Urinary IL-2 and /IL-10 were measured by ELISA in 39 patients receiving BCG for superficial bladder cancer or carcinoma in situ. Measurements were made after each instillation of 81 mg of BCG Connaught (Immucyst) during the induction course and the 3-week maintenance therapy (given at 3, 6, 12, 18, 24, 30 and 36 months). Cytokine levels were correlated with the risk of recurrence, progression, leukocyturia and adverse events. Median follow-up was 35 months (range 7-72 months). Complete responses to BCG were obtained in 30 patients (77%); the remaining 9 patients relapsed (23%), and 4 of these patients progressed (10.2%). Failure to detect urinary IL-2 during BCG induction course and the first extended induction cycle (6+3 schedule) correlated with time to recurrence (p = 0.01) and progression (p = 0.01). During the extended induction cycle, the first instillation was associated with an IL-2 cytokine profile, whereas the second and third instillations were associated with a switch to an IL-10 cytokine profile. This switch was associated with leukocyturia (p = 0.0001) and adverse events (p = 0.03). The 6+3 schedule is associated with urinary IL-2 overproduction and improved recurrence- and progression-free survival. During the BCG extended induction cycle, the favorable IL-2 urinary cytokine pattern gradually switches to an IL-10 profile, suggesting that the schedule based on 3 weekly instillations may be unsuitable for some patients and that the dose and frequency of maintenance BCG instillations may be adapted to individual urinary cytokine levels.

Prognostic value of a T helper 1 urinary cytokine response after intravesical bacillus Calmette-Guerin treatment for superficial bladder cancer.

PURPOSE: Interleukin (IL)-2 and interferon-gamma are released during T helper 1 lymphocyte responses, while IL-10 is released during T helper 2 responses. We evaluated the prognostic value of urinary IL-2, interferon-gamma and IL-10 levels in patients with superficial bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation. METHODS: Urinary IL-2, interferon-gamma and IL-10 were measured by enzyme-linked immunosorbent assay in 37 patients receiving BCG for stages Ta/T1 superficial bladder cancer, and carcinoma in situ. Measurements were made after instillations 5 and 6 during a course of 6 weekly instillations of 150 mg. BCG, Pasteur strain. Correlations of cytokine levels with the clinical outcome were evaluated using the log rank test. RESULTS: Median followup was 29 months. Patients with urinary IL-2 less than 27 pg./micromol. creatinine were significantly more likely to have recurrences than those with higher values (log rank test p = 0.0009). Urinary IL-10 and interferon-gamma levels had no apparent impact on the risk of recurrence or progression. CONCLUSION: Urinary IL-2 levels may serve to identify patients at risk for bladder cancer recurrence after a single course of BCG and, thus, to tailor individual treatment.